Future Neuroprotective Approach In Strokes Biology Essay

Stroke is the 3rd largest cause of decease next to bosom disease and malignant neoplastic disease in the western universe. About 5.5 million people died from shot in 1999. In USA, the incidence of shot is estimated about 750,000 per annum ( www.stroke.org ) , with a mortality of 150,000 per annum. The altering form of diseases happening in India due to attempts in control of catching diseases have brought in a crisp focal point, stroke as one of the major wellness jobs.

Recent community studies from many parts of India show a prevalence rate presumed to be in the scope of 40 to 270/100,000 in rural population as compared to the reported prevalence of 400-800/100,000 in metropolitan metropoliss [ 1-3 ] . Males are more susceptible to ischemia as compared to females with a ratio of 1.7.

Stroke occurs as a consequence of break of blood supply to a portion of encephalon typically by a thrombus occlusion or embolus or bleeding due to rupture of blood vass. The symptoms of shot scopes from blurred vision to vertigo, giddiness, paroxysm, and loss of consciousness depending on the country of the nervous system affected. There are broad scopes of motor and sensorimotor shortages, including shudder, deficiency of co-ordination and partial or complete palsy. Major disablement consequences from lose of ability to pass on, ambulate, co-ordinate or ground. Many hazard factors have been identified as the likely cause for ischaemia. The non-modifiable factors include age, gender, positive household history, ethnicity, old transient ischaemic onslaught or shot whereas, the modifiable factors include high blood pressure, diabetes, smoke, lipid upsets – hypercholestrolemia, intoxicant poisoning and physical inaction.

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Treatment options are limited to supportive attention and the direction of complications. Currently merely approved drug for shot is endovenous recombinant tissue plasminogen activator ( rtPA ) and is effectual within 3 hours of oncoming of shot. Because of narrow curative window, it can be used in a really little per centum of acute shot patients. Despite significant research into neuroprotection, there is no sanctioned therapy, which can cut down stroke size or neurological disablement. The pathophysiology involved in ischaemic shot is complex and non yet to the full understood [ 4-6 ] . The development of new curative attacks therefore remains a important challenge. Engagement of assorted neurotransmitters and neuromodulators have been shown to lend to the ischaemic hurt and neural decease associated with shot [ 7 ] . Role of excitatory amino acid receptor activation, Ca overload, azotic oxide, and oxidative emphasis in the pathogenesis of ischaemic encephalon harm is good established ( Fig. 1 ) . Several curative schemes bothA in vitroA andA in vivoA suppressing excitant amino acid receptor activation, Ca overload and oxidative emphasis have been explored. A figure of experimental agents cut down infarction size in well-controlled carnal shot theoretical accounts have failed to demo efficaciousness in clinical surveies. The failure of neuroprotective drugs in the clinic has been tentatively attributed to several factors such as toxicity, narrow curative clip window, trouble in happening a clinically relevant bringing system to administrate compounds intracerebrally over a long period of clip and trouble in permuting standardised experimental scenes to human state of affairss. Several new schemes are presently emerging, based on recent progresss in our apprehension of molecular tracts that could be considered as possible curative marks. These marks includes free groups, poly ( ADP ribose ) polymerase, apoptotic, mitogen activated protein kinases, growing factors and cistron activations.

Fig. 1: Mechanisms of neural decease in shot: Break of intellectual blood flow consequences in reduced energy production, which causes failure of ionic pumps, release of excitant neurotransmitter such as glutamate from presynaptic terminuss and coevals of free groups. These events activate downstream signaling cascade such as PARP and MAP kinases taking to cell decease. ROS-reactive O species, PARP – poly ( ADP ribose ) polymerase, MAP kinases-mitogen activated protein kinases.

Antioxidants and Poly ( ADP-ribose ) polymerase inhibitors

The cardinal nervous system is peculiarly vulnerable to oxidative harm caused by free groups and their toxic effects on the encephalon are diverse. Degrees of endogenous antioxidant enzymes fall during ischaemia where as free extremist production additions during reperfusion. Free groups such as superoxide, hydroxyl, and azotic oxide are involved in the pathophysiology of intellectual ischaemia. Nitric oxide, which is a weak extremist that can unite with superoxide to organize a more toxic species Peroxynitrite [ 8 ] . Peroxynitrite is a powerful oxidizer that induces an array of hurtful events including peroxidation of membrane lipoids, depletion of glutathione, DNA individual strand breakage, and chondriosomes disfunction and cell decease [ 9 ] . Peroxynitrite production depends on the phase of development of the ischaemic procedure and on the cell type bring forthing azotic oxide. Recent grounds study that peroxynirite may besides move as signaling molecule by advancing phospholipase A2 and release of arachadonic acid. Antioxidants such as tirilazad mesylate and ebselen have been tried in animate beings and worlds. We have demonstrated the neuroprotective effects of antioxidants { metalloporphyrin catalytic antioxidants ( FeTMPyP and FeTPPS ) and Curcumin } in intellectual ischaemia theoretical account [ 10-13 ] .

Free groups induced DNA dents can take to over activation of Poly ( ADP-ribose ) polymerase ( PARP ) . Though PARP play function in keeping genomic unity and in the fix of DNA strand interruptions. However, overactivation of PARP in shot utilizes NAD taking to depletion of NAD and accordingly ATP depletion [ 14 ] . Energy depletion in already energy starved ischaemic nerve cell consequences in cellular disfunctions taking to cell decease. Therefore suppressing PARP may be good effects in the intervention of shot. There are several studies bespeaking the curative potency of PARP inhibitors in neural hurt [ 15,16 ] . We have demonstrated neuroprotective consequence of PARP inhibitors such as nicotinamide, 3-aminobenzamide, 4-Amino 1, 8-Napthalimide [ 17 ] and 1, 5-isoquinolidiol in focal intellectual ischaemia model.A These agents have shown to protect cells against N-methyl-D-aspartate, azotic oxide, and peroxynitrite induced cytotoxicity and DNA harm. They can forestall depletion of NAD and protect against reduced production of ATP in ischaemic encephalon. 4- nicotinamide and 4-amino 1, 8-napthalimide have shown to protect against mortification and apoptotic cell decease. There are several PARP inhibitors, which are under clinical development for neurological upsets.

MAP Kinase Inhibitors

Mitogen-activated protein kinase ( MAPK ) tracts are major signaling cascade commanding complex programmes such as embryogenesis, distinction, and cell decease in add-on to short-run alterations required for homeostasis and hormonal response. There are three tracts consist of kinase Cascadess taking to activation of ERKs ( Extracellular signal Regulated protein Kinases ) , JNKs ( c-Jun N-terminal kinases ) and p38/CSBP protein kinases. Both JNKs and p38 tracts are involved in relaying emphasis type extracellular signals.

The ERK tract is chiefly responsible for transducing mitogenic differential signals to the cell nucleus. ERKs household protein kinase includes chiefly ERK1, ERK2. Activation of ERK1/2 is of import for the several neural maps like neural distinction, and endurance during development and adaptative response of mature nerve cells. There are groundss of activation of ERK1/2 after intellectual ischaemia [ 18 ] . Several inhibitors of MAPK cascade such as PD98059 and U0126 have been tried for neuroprotection and showed neuroprotective in carnal theoretical accounts.

Activation of the JNK/SAPK tract has besides been shown to be increased after transeunt intellectual ischaemia and planetary ischaemia. Three isoforms of JNK viz JNK1, JNK2 and JNK3 have been identified. JNK1 and JNK2 are found in all tissues, whereas JNK3 is found most abundant in encephalon, bosom and testicle. JNK activity is increased as early 3 hours after transeunt MCAO and farther increased up to 72 hours. The translocation of activated JNKs into the karyon is controlled by JIPs ( JNK-interacting proteins The regulator of JIP-1 has been shown to forestall neural cell decease. Under experimental status PD98059, U0126 inhibit both ERK and JNK. The activity of p38 inhibitor such as SB-203580 may be explained by suppression of JNK2 and/or JNK3. CEP1347 inhibits JNK pathway nevertheless activates ERK tract. Recently more selective JNK inhibitors have been generated, which includes SP600125 and SP69766.

p38 is widely distributed in mammalian tissue including encephalon. p38 tract dramas of import function in transducing signals involved in cell endurance, programmed cell death and inflammatory cytokine production. Sustained activation of p38 has been shown to be associated with neural cell death/apoptosis and selective p38 inhibitors have been shown to advance cell endurance. The p38 tract is strongly activated by factors such as TNF-Aµ and interleukin-1b, which is known to be increased after shot and have been shown to be involved in the mechanism underlying ischaemia, induced cell decease. Increased p38 activity is reported after intellectual ischaemia. Extensive survey has been done on p38 inhibitors induced neuroprotection in ischaemia [ 19 ] . More convincing informations back uping the theoryA that p38 suppression provides neuroprotection after CNS hurt utilizing new coevals potent p38 inhibitor SB-239063 have been reported.

Antiapoptotic agents

Despite an intuitive nexus between ischaemic abuses and mortification, turning grounds indicates that programmed cell decease culminating in programmed cell death may besides lend to ischemia induced delayed neural loss [ 20 ] . Apoptosis is extremely orchestrated signifier of cell decease in which cells neatly commit suicide by chopping themselves into membrane-packed spots. The bcl-2 household of protein is a chief protein modulating programmed cell death. In Bcl-2 household, BCL-X is the ant-apoptotic proteins where as Bax, Bid, Bad are proapoptotic in nature. Bcl-2 protects the cortical nerve cells in mice from ischaemic abuse induced by lasting in-between intellectual arteria occlusion [ 21 ] . Bad, a proapoptotic protein displaces bax from bcl-2 or bcl-xl heterodimer, leting free Bax to transport out its decease promoting maps [ 22 ] . Bid promotes apoptosis through its binding to Bax. Bid is cleaved by caspase-8 and cleavage fragment translocates from cytosol to mitochondrial membrane where it induces a structural alterations to bax verification taking to cytochrome hundred release, taking to activation of executing caspase. The transgenic mice that overexpressed bcl-2 in nerve cells had significantly smaller infarction. Bid deficient mice showed less infarction volume in which caspase, cytochrome-c look is badly impaired. The inhibitor of programmed cell death ( IAP ) household of proteins, which includes the neural programmed cell death inhibitory protein ( NAIP ) , the X-chromosome-linked IAP ( XIAP ) , and human IAP-1 and -2, constitute cellular regulators of cell decease that are really well-conserved across species.A XIAP is the most powerful inhibitor in the household, and protects against programmed cell death by adhering to caspases.

Caspases ( cysteine peptidases ) are proteolytic enzymes plays cardinal function in the induction and executing of the apoptotic plan. All caspases are expressed as pro-caspases. Once activated caspases cleaves proteins in a comparatively substrate specific mode. Caspases are activated by a ) cytokine mediated receptor activation and B ) via change of mitochondrial membrane potency. Caspase activation is of course controlled by a set of endogenous molecules shacking in the cytosol and in the chondriosome. A twelve of caspases are found till now, amongst caspase 3 plays a major function in programmed cell death. Caspase 3 has highest homology to ced-3, the cardinal peptidase found in programmed cell decease, is expressed in CA-1 nerve cells after intellectual ischaemia. Activation of caspase-3 has been demonstrated in IR hurt. Inhibitors of caspases were found to cut down the infarction suggests that blocked of the apoptotic tract prevents the nerve cells from apoptotic cell decease. Caspase irreversible inhibitors z-VAD and z-devd significantly diminish cortical infarction in reasonably terrible but transeunt prosencephalon and focal ischaemic abuses in rat. Z-VAD fmk ( z-Val-Ala-Dl-Asp-fluoromethyl ketone ) a broad-spectrum caspase inhibitor showed neuroprotection in carnal theoretical account of focal and planetary ischaemia. Caspase suppression holds enormous neuroprotective potency. Small molecule inhibitors are actively being developed by the pharmaceutical industry. Peptide-based inhibitors may continue cellular functionality, but merely in the short period following ischaemic daze, and non in all cases.A Other obstructions include safety, encephalon incursion, and caspase selectivity, authority, and pharmacokinetic belongingss. Broad-range inhibitors may interact with critical cysteine peptidases, ensuing in the deregulating of programmed cell death, but may besides impact critical maps, overloading the cell decease tracts and exchanging the result from programmed cell death to mortification.

Suppressing Phosphatidylinositol 3-kinase ( PI3-K ) /Akt ( protein kinase B ) tract

Recently it has been demonstrated that PI3-K/Akt and downstream phosphorylated Bad and proline-rich Akt substrate endurance signaling tracts are upregulated in lasting nerve cells in the ischaemic encephalon that overexpresses copper-zinc superoxide dismutase activity. Surveies of Chan group [ 23 ] have provided another fresh curative marks in neuroprotective schemes in shot.

Growth factors

In nervous system growing factors stimulate distinction ( during development ) , support neural endurance and by and large considered to be neuroprotective. Several growing factors are expressed during intellectual ischaemia including BDNF, NGF, bFGF, PDGF, TGFb and VEGF. Upregulation of messenger RNA encoding BDNF and NGF have been observed in dentate granule cells even after brief ischaemia. Many presymptomatic proved the outstanding betterment on intervention with growing factors after ischaemic abuse [ 24 ] . The mechanism by which growing factors protect nerve cells after shot has been debated. Basic fibroblast growing factor has been reported to protect nerve cells inA inA vitroA andA in vivoA against excitotoxicity, ROS and toxins induced abuses. Clinical tests were conducted to measure the neuroprotective potency of bFGF in shot patients based on the presymptomatic studies. However, in clinical surveies the intervention seems to be worthless and did non change the mortality rate in patients. In some surveies the built-in antigenic belongings of growing factors resulted in immune reactions ( decrease in average blood force per unit area and leucocytosis ) .

Gene therapy

Accretion of glutamate in the extracellular infinite and [ Ca++ ] iA overload in nerve cells activates many downstream procedures including cistron written text. Distribution and cellular specificity of these responses strongly depend on the continuance and badness of the IR abuse. More than 100 cistrons which are denoted as immediate early cistrons ( IEG ) have been reported to be expressed within 15 min. of the abuse. These include many proteins ( eg. cytokines, enzymes, written text factors etc. ) . Transcription factorsA c-fos, fos-B, c-junA andA junDA are transforming genes, which are involved in the transcriptional activation of other cistrons. Heat daze cistrons are activated continuously or instantly after the IEG look to stabilise the stressed cells. As figure of possible cistron campaigners such as calbindin D28K, glucose transporter, HSP72, interleukin-1 receptor adversary, interleukin-10, transforming growing factor-I?1, glial cell line derived neurotrophin factor, hepatocyte growing factor, Bcl2, nervous programmed cell death inhibitory protein and oxidation-reduction inducible antioxidant protein have been implicated in intellectual infarction bespeaking that cistron therapy could be one of the most promising therapy and will hold several advantage over classical drug therapies. There has been a job that drug proteins are unable or hard to go through through blood encephalon barrier. In cistron therapy, nevertheless, drug proteins are expressed in the encephalon with transgene transportation technique. Furthermore, the development of new vectors and cistron bringing systems has been studied. Herpes Simplex is considered to as one of the common vector systems used to present the cistrons to nervous system. Many proteins have been experimented to measure the neuroprotective possible inA inA vitroA andA in vivoA theoretical accounts of IR hurt. Upregulation of glucose transporter-1 as a consequence of transient transfection utilizing herpes simplex vector system resulted in important betterment in neural endurance after focal ischaemia. The other proteins that are tried include heat daze protein ( HSP70 ) [ 25 ] and calmodulin ( Ca++A adhering protein ) . Gene therapy aimed to upregulate these proteins produced conflicting consequences. HSP70 over look failed to bring forth protection against excitotoxicity induced neural loss in primary neural civilizations. Nevertheless it produced neuroprotection on intervention 20 min. after MCAO induced ischemia theoretical account of shot in rat. Herpes simplex virus mediated transfection of calmodulin cistron resulted in decrease of neural loss. In similar attack many other cistrons that are involved in apoptotic neural loss have besides been experimented. The safety of the vectors is considered to an of import modification factor for the cistron therapy in human existences. Gene therapy would be a strong scheme for intervention of intellectual infarction in the hereafter.

Decisions

Despite the important figure of neuroprotective drugs that have been developed to restrict ischaemic encephalon harm and better the result for shot patients, ischaemic shot is still a prima cause of decease and long-run disablement. Several clinical surveies with neuroprotective agents are still in advancement and we are waiting for these surveies outcome ( Table 1 ) . The pathophysiological mechanisms taking to the neural decease are so complex that individual mechanism based neuroprotective agent has ne’er been shown sufficiently cut down intellectual infarction in human. A scheme of utilizing the combination of the neuroprotective agents in the intervention of shot demands to be explored [ 26 ] . Therefore, it would be a blunt attack to aim drugs, which act by different mechanism at the same time to restrict ischaemic hurt. In add-on to neuroprotective drugs and their combination, schemes aimed at heightening endogenous neural malleability or replacing dead cells or damaged nerve cells utilizing root cell organ transplant may be explored for shot.

Table 1: Ongoing clinical tests for shot

Sr. No

Drug Name

Class

Development Status

1

MLN-519

Protease inhibitor

Phase I

2

Neural cells

Root cell

Phase I

3

CS-747

ADP receptors antagonist

Phase I

4

249417

Anti-factor IX MAb

Phase I

5

Neptunium 1506 ( delucemine )

NMDA adversary

Phase I

6

Troxoprodil ( CP-101,606 )

NMDA adversary

Phase II

7

234551

Endothelin A adversary

Phase II

8

737004 ( S-0139 )

Endothelin A adversary

Phase II

9

Zonampanel ( YM872 )

AMPA adversary

Phase II

10

ReoPro ( abciximab )

GPIIa/IIIb adversary

Phase II completed

11

Repinotan HCI

5HT1 adversary

Phase II/III

12

Cerovive ( NXY-059 )

Free extremist scavenger

Phase II/III

13

Citicoline

Phasphaticholine precursor

Phase IIIReferences

[ 1 ] Anand, K. ; Chowdhury, D. ; Singh, K.B. ; Pandav, C.S. ; Kapoor, S.K. Appraisal of mortality and morbidity due to shots in India. Neuroepidemiology. 20: 208-11. ; 2001.

[ 2 ] Dhamija, R.K. ; Dhamija, S.B. Prevalence of shot in rural community — an overview of Indian experience. J Assoc Physicians India. 46: 351-4. ; 1998.

[ 3 ] Dalal, P.M. Stroke in India: issues in primary and secondary bar. Neurol India. 50 Suppl: S2-7. ; 2002.

[ 4 ] Lo, E.H. ; Dalkara, T. ; Moskowitz, M.A. Mechanisms, challenges and chances in shot. Nat Rev Neurosci. 4: 399-415. ; 2003.

[ 5 ] Fisher, M. ; Brott, T.G. Emerging therapies for acute ischaemic shot: new therapies on test. Stroke. 34: 359-61. ; 2003.

[ 6 ] Onteniente, B. ; Rasika, S. ; Benchoua, A. ; Guegan, C. Molecular tracts in intellectual ischaemia: cues to fresh curative schemes. Mol Neurobiol. 27: 33-72. ; 2003.

[ 7 ] Koroshetz, W.J. ; Moskowitz, M.A. Emerging interventions for shot in worlds. Tendencies Pharmacol Sci. 17: 227-33. ; 1996.

[ 8 ] Forman, L.J. ; Liu, P. ; Nagele, R.G. ; Yin, K. ; Wong, P.Y. Augmentation of azotic oxide, superoxide, and peroxynitrite production during intellectual ischaemia and reperfusion in the rat. Neurochem Res. 23: 141-8. ; 1998.

[ 9 ] Virag, L. ; Szabo, E. ; Gergely, P. ; Szabo, C. Peroxynitrite-induced cytotoxicity: mechanism and chances for intercession. Toxicol Lett. 140-141: 113-24. ; 2003.

[ 10 ] Thiyagarajan, M. ; Kaul, C.L. ; Sharma, S.S. Neuroprotective efficaciousness and curative clip window of peroxynitrite decomposition accelerators in focal intellectual ischaemia in rats. Br J Pharmacol. 142: 899-911. Epub 2004 Jun 14. ; 2004.

[ 11 ] Thiyagarajan, M. ; Sharma, S.S. Neuroprotective consequence of curcumin in in-between intellectual arteria occlusion induced focal intellectual ischaemia in rats. Life Sci. 74: 969-85. ; 2004.

[ 12 ] Gupta, S. ; Kaul, C.L. ; Sharma, S.S. Neuroprotective consequence of combination of poly ( ADP-ribose ) polymerase inhibitor and antioxidant in in-between intellectual arteria occlusion induced focal ischaemia in rats. Neurol Res. 26: 103-7. ; 2004.

[ 13 ] Gupta, Y.K. ; Chaudhary, G. ; Sinha, K. Enhanced protection by melatonin and meloxicam combination in a in-between intellectual arteria occlusion theoretical account of acute ischaemic shot in rat. Can J Physiol Pharmacol. 80: 210-7. ; 2002.

[ 14 ] Endres, M. ; Wang, Z.Q. ; Namura, S. ; Waeber, C. ; Moskowitz, M.A. Ischemic encephalon hurt is mediated by the activation of poly ( ADP-ribose ) polymerase. J Cereb Blood Flow Metab. 17: 1143-51. ; 1997.

[ 15 ] Virag, L. ; Szabo, C. The curative potency of poly ( ADP-ribose ) polymerase inhibitors. Pharmacol Rev. 54: 375-429. ; 2002.

[ 16 ] Pieper, A.A. ; Verma, A. ; Zhang, J. ; Snyder, S.H. Poly ( ADP-ribose ) polymerase, azotic oxide and cell decease. Trends Pharmacol Sci. 20: 171-81. ; 1999.

[ 17 ] Kabra, D.G. ; Thiyagarajan, M. ; Kaul, C.L. ; Sharma, S.S. Neuroprotective consequence of 4-amino-1,8-napthalimide, a poly ( ADP ribose ) polymerase inhibitor in in-between intellectual arteria occlusion-induced focal intellectual ischaemia in rat. Brain Res Bull. 62: 425-33. ; 2004.

[ 18 ] Hu, B.R. ; Liu, C.L. ; Park, D.J. Alteration of MAP kinase pathways after transient prosencephalon ischaemia. J Cereb Blood Flow Metab. 20: 1089-95. ; 2000.

[ 19 ] Legos, J.J. ; McLaughlin, B. ; Skaper, S.D. ; Strijbos, P.J. ; Parsons, A.A. ; Aizenman, E. ; Herin, G.A. ; Barone, F.C. ; Erhardt, J.A. The selective p38 inhibitor SB-239063 protects primary nerve cells from mild to chair excitotoxic hurt. Eur J Pharmacol. 447: 37-42. ; 2002.

[ 20 ] Graham, S.H. ; Chen, J. Programmed cell decease in intellectual ischaemia. J Cereb Blood Flow Metab. 21: 99-109. ; 2001.

[ 21 ] Kane, D.J. ; Sarafian, T.A. ; Anton, R. ; Hahn, H. ; Gralla, E.B. ; Valentine, J.S. ; Ord, T. ; Bredesen, D.E. Bcl-2 suppression of nervous decease: reduced coevals of reactive O species. Science. 262: 1274-7. ; 1993.

[ 22 ] Yin, X.M. ; Luo, Y. ; Cao, G. ; Bai, L. ; Pei, W. ; Kuharsky, D.K. ; Chen, J. Bid-mediated mitochondrial tract is critical to ischemic neural programmed cell death and focal intellectual ischaemia. J Biol Chem. 277: 42074-81. Epub 2002 Aug 27. ; 2002.

[ 23 ] Chan, P.H. Future marks and Cascadess for neuroprotective schemes. Stroke. 35: 2748-50. Epub 2004 Sep 23. ; 2004.

[ 24 ] Kawamata, T. ; Dietrich, W.D. ; Schallert, T. ; Gotts, J.E. ; Cocke, R.R. ; Benowitz, L.I. ; Finklestein, S.P. Intracisternal basic fibroblast growing factor enhances functional recovery and up-regulates the look of a molecular marker of neural shooting following focal intellectual infarction. Proc Natl Acad Sci U S A. 94: 8179-84. ; 1997.

[ 25 ] Yenari, M.A. ; Giffard, R.G. ; Sapolsky, R.M. ; Steinberg, G.K. The neuroprotective potency of heat daze protein 70 ( HSP70 ) . Mol Med Today. 5: 525-31. ; 1999.

[ 26 ] Schmid-Elsaesser, R. ; Hungerhuber, E. ; Zausinger, S. ; Baethmann, A. ; Reulen, H.J. Combination drug therapy and mild hypothermia: a promising intervention scheme for reversible, focal intellectual ischaemia. Stroke. 30: 1891-9. ; 1999.

Ravinder K. Kaundal and Shyam S. Sharma *

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research ( NIPER ) , S.A.S. Nagar ( Mohali ) -160062, Punjab, INDIA

Dr. SharmaA is presently Associate Professor, Pharmacology and Toxicology at National Institute of Pharmaceutical Education and Research ( NIPER ) , Punjab, India. Before fall ining NIPER he worked as Senior Research Associate in 1997 at Department of Pharmacology, All India Institute of Medical Sciences ( AIIMS ) , New Delhi. He worked as postdoctoral chap at Department of Pharmacodynamics College of Pharmacy, The University of Illinois at Chicago, Chicago, USA. He did his Ph.d. from AIIMS, New Delhi in 1998 and M. Pharm. ( Pharmacology ) from College of Pharmacy, New Delhi in 1991.

Dr. Sharma is presently involved in drug find research with major involvements in diseases countries such as shot, diabetic neuropathy and Leishmania. He has worked extensively on engagement of oxidative emphasis, poly ( ADP ribose ) polymerase and MAP kinase tract in shot and diabetic neuropathy. He has more than 20 documents in peer-reviewed scientific diaries and presented 40 documents in several national and international conferences. He has guided more than 15 Masterss and PhD pupils.

He is editor ofA Current Research and Information on Pharmaceutical SciencesA ( CRIPS ) and a life member of the Indian Pharmacological Society ( IPS ) . *corresponding author electronic mail: sssharma @ niper.ac.in, shyamsharma14 @ yahoo.com

A

Stroke: The Neglected Epidemic, an Indian position

PK SethiA

Department of Neurology

Sir Ganga Ram Hospital, Rajinder NagarA A

I AnandA

Department of Neurology

Sir Ganga Ram Hospital, Rajinder NagarA A

R RanjanA

Department of Neurology

Sir Ganga Ram Hospital, Rajinder NagarA A

NK SethiA

Department of Neurology

Weill Cornell Medical CenterA A

J TorgovnickA

Department of Neurology

Saint Vincent ‘s Hospital and Medical CentersA A

Citation: A P. Sethi, I. Anand, R. Ranjan, N. Sethi & A ; J. Torgovnick: Stroke: The Neglected Epidemic, an Indian position.A The Internet Journal of Neurology.A 2007 Volume 8 Number 1

Table of Contentss

Stroke in India

Address for correspondence

Abstraction

It is good known that in most developed states cerebrovascular disease ( CVD ) or shot is a common cause of decease and disablement. In U.S.A. and U.K. , stroke ranks 3rd as a cause of decease after bosom disease and malignant neoplastic disease. The one-year economic effect due to CVD has been estimated to transcend 7 billion dollars in USA1, A 2. Prevalence rates reported for cerebrovascular accident ( CVA ) worldwide vary between 500 to 800 per 100,000 population. Oriental surveies have shown higher prevalence and incidence rates.1A Cherished small is known about the epidemiology of shot in India and of the Indian subcontinent in general. Is this burden same as in the West? Expectation rate of 600 in the West and possibly 900 in East for the prevalence seems pausible1.

Do we have adequate informations to gauge the load of shot in India? India ‘s population is one billion plus, taking a prevalence rate of 900 per 100,000 into history, shot is so so happening in epidemic proportions in India. It is a affair of sorrow that our cognition about epidemiology of shot in India is so hapless. So if shot is happening in epidemic proportions, so so it is a ignored epidemic.

Stroke in India

Epidemiology, originally signified the survey of epidemics, but it is now used more loosely for the survey of groups: epi=among ; demos= people ; logos=study. India is a huge state with diverse geographic fluctuation. The population stands above one billion and life manner of people varies in different parts of the state. It is a multiethnic, multi-cultural, multi-religious society. There are many faiths religious orders with different life manners. Food wonts vary in different spiritual groups. Some like the Jains and Buddhists are rigorous vegetarians while meat and meat merchandises are an built-in portion of the diet of the Sikhs and Punjabis. Some literally drink “ Ghee ” a native cookery oil rich in concentrated fats. Some boulder clay late have non used salt in cooking as people from Mizoram. Some do n’t smoke but alternatively eat baccy. It would be interesting and extremely educative to analyze the epidemiology of shot in such a diverse group.

Unfortunately in India, epidemiological information on one-year incidence, prevalence rates, morbidity and mortality tendencies in good defined populations is non available. Most of informations published is from retrospective analysis of topics admitted to urban medical infirmaries though the bulk of Indian population lives in little towns and small towns. Some of the surveies lack proper shot nomenclature and baseline probes.

Despite these restrictions, analysis of informations collected from major urban infirmaries suggests that about 2 % of all hospital admittances ; 4-5 % of medical and 20 % of neurological admittance have CVD. The incidence of shot in the immature ( & lt ; 40 old ages of age ) is high ( 13 to 32 % ) when compared to similar informations from the West. Literature is available proposing that hazard of coronary arteria disease ( CAD ) is higher in Indians specially in the immature population.3,4,5,6A We know that the hazard factors for shot and coronary arteria disease are same. We besides know that coronary arteria disease is being reported more and more in people of Indian beginning, whether remaining in India or abroad, as compared to Western population. Will it so be just to presume that incidence of shot and its prevalence may be higher in Indians excessively? A 3, A 4, A 5

Many surveies on epidemiology of shot in India are lacking with regard to randomisation of informations, doing comparing between them hard. In add-on, many of these surveies are published in local diaries, which are non indexed and hence hard to recover from, or have been merely published as abstracts. Table I presents a sum-up of rough prevalence rate by study of unilateral paralysis presumed to be CVD from different parts of India viz. the North, South, West and east7,8,9,10,11,12,13,14,15,16A This information show prevalence of CVD in the scope of 52 to 843 per 100,000 population. Merely information from the Paris Community ( Bombay ) , ( 843/100,000 ) comes someplace near the expected rate of 900/100,000 in the oriental population. Lower rate reported in other surveies may be due to several factors. In some lone unilateral paralysis was taken as a rough index of shot. Further, possibly the method of aggregation of public wellness informations was faulty.

In India, peculiarly in rural countries, the wellness attention bringing system is still lacking, both in quality and coverage. Accurate and current nose count informations is non available, and the figure of good trained doctors and wellness workers are limited, rendering the proper survey of neuroepidemiology of CVD hard. As we do non cognize the existent load of assorted diseases, planning of wellness services and distribution of resources is hard and at times an educated conjecture at the best.

A

Table 1: Bharat: Crude Prevalence Rate By Survey Of Hemiplegia Presumed To Be CVA.

Another dramatic thing in India is the deficiency of consciousness about shot and shot bar. The biggest thing which has happened to stroke and its direction In India is non tPA instead coining of the word “ Brain Attack ” . For a alteration brain doctors left their tusk towers and spoke in a layperson ‘s linguistic communication. Unless people know what disease we are speaking about, one can non roll up any meaningful epidemiological informations or speak about bar of the disease. The best intervention of shot still remains its bar. For every talk a neurologist gives on tPA he should give at least ten on primary and secondary bar of shot. We are already paying a heavy monetary value for carelessness of this simple fact. What about carelessness on portion of the patient? Indians, by big, are non wellness witting. There is no societal security system and no worthwhile wellness insurance. The feeling is that some how their “ Karma ” will salvage them from disease or if unluckily they fall ill, God shall look after them.

India may be a hapless state but it is rich in computing machine hardware and package engineering. Computers are quickly distributing to towns and small towns. Medical governments with the aid of the mass-media should do interesting plans to educate people about shot, its warning marks and how to forestall it. Educating of the multitudes should be the primary end. Neurological associations and societies should hold a patient forum to convey this message to the populace. Once this is achieved, we shall be in an first-class place to analyze the epidemiology of this epidemic, till so this epidemic remains mostly neglected.

Address for correspondence

NK Sethi, MD

Department of Neurology

Weill Cornell Medical Center

New York, NY 10021

Electronic mail: A [ sethinitinmd @ hotmail.com ]