Jain et al: Cerebroprotein hydrolysate IJMDS www.ijmds.org January 2014; 3(1)382 Educational Forum Cerebroproteinhydrolysate: Innovation in Neurodegenerative disorders Jain N1, Yadav S2, Goyal M3, Singal KK4, Gupta P5, Bansal M6 ABSTRACT Stroke,traumaticbraininjuryandneurodegenerativedisordersareoneofthe leadingcausesofdeathanddisabilityinbothdevelopinganddeveloped countries.Anumberofdrugsincludingneurotrophicdrugsareavailablefor these disorders. Cerebroprotein hydrolysate is the latest one offering new hopes to patients suffering from these disorders. Its superiority is because of different actionswhichhelpinfasterandmorecompletenerverepairandgrowththan otherneurotrophicagents.Itactsbymultiplemechanismsviz.-regulationand improvementoftheneuronalmetabolism,modulationofthesynaptic plasticity,promotingneuronaldifferentiationandprotectionagainstischemic and neurotoxin lesion, reducing excitotoxic damage, blocking over activation of calcium dependent proteases, and scavenging free oxygen radicals. Till now no serious adversity has been reported. Keywords:Neurodegenarativedisorders,cerebroproteinhydrolysate, neurotrophic factors, calpain Epidemiologic Considerations Ischemicstroke,traumaticbraininjury, vasculardementiaandAlzheimersdisease collectively are responsible for major part of morbidityandmortalityingeriatricaswell asyoungadultpopulation.Strokeranksas thethirdleadingcauseofdeathinthe United States. It is estimated that there are morethan700000incidentsofstrokes happeningannuallyand4.4millionstroke survivors. [1]InUSAonanaverage, approximately1.7millionpeoplesustaina traumatic brain injury annually. [2]
Inastudyitisfoundthatonan average,intheUSA,1300/100,000people sufferconcussionseachyear. [3]Outof thosewhoreceivetreatment25patients die. Neurodegenerative diseases that affect theaffective,cognitiveandpsychomotor functionsintheelderlycompromisethe qualityoflifeofmorethan24million peopleacrossthe world. [4]Thesedisorders posesomeofmodernmedicinesmost difficultchallenges.Common pathophysiologicfeatureinallofthese conditionsissamei.e.functionallossof neurons. Pathophysiology of neuronNeuronisthebasicstructuraland functional unit of nervous system. Although there are some variations depending on the 1Dr Nidhi Jain Associate Professor, Pathology 2Dr Shailesh Yadav Professor, Pharmacology 3Dr Manoj Goyal Associate Professor, Pharmacology 4Dr Kiran Kumar Singal Assistant Professor,Medicine 5Dr ParveenGupta Assistant Professor,Medicine 6Dr Monika Bansal Associate Professor, Physiology 1,2,3,4,5,6MMIMSR Mullana, Ambala, Haryana, India Received: 07-09-2013 Revised: 10-10-2013 Accepted: 06-11-2013 Correspondence to Dr Shailesh Yadav 09050365854 [email protected] Jain et al: Cerebroprotein hydrolysate IJMDS www.ijmds.org January 2014; 3(1)383 type of neurons; they all contain four parts: cellbody,dendrites,axonandaxon terminal.Theydevelopfromtheneural stemcellsknownastype1cellswhich produceprogenycalledamplifyingneural progenitor cells (also known as type 2 cells) whichproliferateanddifferentiateinto matureneurons.Tillrecentpastitwas believedthatthereisnowaytorepaira damagedneuron.Oneofthemaingoalsof researchersinvolvedintreatmentof neurodegenerativedisordersistodevelop drugstostimulatenerverepairitself. [5] SeveraldrugslikeEdaravone,Citicolineand Piracetamhavebeendevelopedbasedon neurotrophicfactors.Neurotrophicfactors aresmallproteinsthatexertsurvival-promotingandtrophicactionsonneuronal cells. [6] These neurotrophic factors are NGF (Nervegrowthfactor),BDNF(Brain-derived neurotrophicfactor),NT-3(Neurotrophin-3),GDNF(Glialcell-derivedneurotrophic factor),GAP-43(growthassociatedprotein 43) and CNFT (Cilliary neurotrophic factor). Glialcellscontinuetoundergocell divisioninadulthoodandtheirabilityto proliferateisparticularlynoticeableafter braininjury(e.gstroke). [7]Thisisnotthe casewithneurons;theycannotdivide themselvesbuttheyundergoalotof activityafterinjury.Interestingly,studies demonstrate that neurons in the adult brain haveanunappreciatedcapacityfor remodelingawayfromtheactualinjury, andthattheseneuronsareattemptingto rewire the brain following an injury. [8] Cerebroproteinhydrolysateisthelatest weaponinthephysiciansarmamentarium. It is a neurotrophic drug. It consists of short biologicalpeptideswhichactlike endogenous neurotrophic factors. Pharmacokinetics It is given in a dose of 60 -180 mg once daily for10-20days.Itshouldbeslowlyinfused in250mlsalinein60-120minutes. Maintenance doses (30 mg) can be given by i.mroute.Itshouldnotbemixedwith aminoacidsolutionsintheinfusionbottle. Doses of antidepressants should be reduced if used with Cerebroprotein hydrolysate. Adverse effects and ContraindicationsStudies [9,10] have revealed that most of the sideeffectsareminor.Mostcommonside effectsincludeheadache,nausea,vertigo, increasedsweating,agitation,fever, hallucinations,confusion,andflulike syndrome.Contraindicationsinclude hypersensitivity,epilepsyandsevererenal impairment.Safetyhasnotbeen established in pregnancy and lactation. Indications Acute ischemic stroke Traumatic brain injury Vascular dementiaAlzheimers disease Mechanismofactionandpharmacological effectsIt acts by multiple mechanisms viz. Regulationandimprovementofthe neuronal metabolism. Modulation of the synaptic plasticity. Neuronaldifferentiationandprotection against ischemic and neurotoxin lesion. Cerebroproteinhydrolysatereduces excitotoxicdamage,blocksoveractivation ofcalciumdependentproteases,and scavenges free oxygen radicals. Cerebroproteinhydrolysatehasbeen showntocounteractthenegativeeffectof Jain et al: Cerebroprotein hydrolysate IJMDS www.ijmds.org January 2014; 3(1)384 theelevatedEGF-2onneurogenesisand neuromodulation. [11]
Cerebroproteinhydrolysate-augmentedproliferation,differentiation, andmigrationofadultsubventricularzone (SVZ)neuralprogenitorcellsresultsin increased number of neural progenitor cells andneuroblaststocontributeto neurogenesis.Thismaybethemechanism for beneficial effect in acute ischemic stroke and traumatic brain injury. Enhancementofneuronalsurvivalis producedthrougheffectoncalpain.The hyper activation of calpain is implicated in a numberofneurodegenerativedisorders. CalpainisinhibitedbyCerebroprotein hydrolysate.Neuromodulatory effect is produced by increasing glucose transporter1 (GLUT-1) expressionwhichisresponsibleformore than90%ofglucosetransporttobrain. [12] Neuronal plasticity is produced by reduction ofamyloidbetaaccumulation,increased MAP 2 and Synaptophysin synthesis. Neuro-immunotrophicactivityisproduced byinhibitionofmicroglialactivationand expressionofIL-1beta.Thisresultsin reductionofinflammation.Other neurotrophicdrugsandnootropicsarenot having so much broad spectrum of different actionspossessedbyCerebroprotein hydrolysate.Thepatientsof neurodegenerativedisordersnowcanbe managed in a better way with the advent of Cerebroprotein hydrolysate. References 1.LarryBG,RobertA,KyraB,CurtDF, PhilipBG,GeorgeHetal.Primary PreventionofIschemicStroke.A StatementforHealthcareProfessionals from the Stroke Council of the American HeartAssociation.Stroke2001;32:280-99. 2.InjuryPrevention&Control:Traumatic BrainInjury.Availablefrom:http:// www.cdc.gov/traumaticbraininjury/. [last accessed on 30-nov-2011]. 3.Aziz-SultanA,BaimeediP,BenzelEC,BergerMS,BrandnerS,ButowskiNetal. Introduction to traumatic brain injury. In Samandouras G, editor. Traumaticbrain injury:TheNeurosurgeon'sHandbook. Isted.Oxford:OxfordUniversityPress; 2010.p.207-8. 4.Sanjeev V Thomas. Addressing problems ofdementiainIndia. Ann Indian AcadNeurol 2011;14:147. 5.Introductiontoneurogenesis.Available fromhttp://www.neurogenesis.iord.org /.[Last accessed on 15th Oct. 2011].6.Availablefrom:http://www.ceregene. com/neurotrophic.asp.[Lastaccessed on 30 Oct. 2011]. 7.BarrettKE,BarmanSM,BoitanoS, BrooksHL.ExcitableTissue:Nerve.In GanongWF,editor.Physiologyofnerve andmusclecells:ReviewofMedical Physiology.23 rded.Lange:McGraw Hill; 2010.p.80. 8.GopalanT.Neurons:KeyToHealingOf BrainInjuriesIdentified.August24, 2010.Research News [online] Available from:http://www.medindia.net/news /Neurons-Key-To-Healing-Of-Brain-Injuries-Identified-73058-2.htm.[Last accessed on Nov 28 2011]. 9.Long J, Wei GZ, Xu ZB, Feng YB. Injection ofcerebroproteinhydrolysatevs Cerebrolysinintreatingcerebrovascular diseases.Availablefrom:http://en. cnki.com.cn/Article_en/CJFDTOTAL-Jain et al: Cerebroprotein hydrolysate IJMDS www.ijmds.org January 2014; 3(1)385 XYYL606.002.htm.[Lastaccessedon March 07 2012].10. SuiCM, KamWC, Jia-HongL, Durairajan SSK, Liang-FengL, MinL.Systematic ReviewontheEfficacyandSafetyof HerbalMedicinesforVascular Dementia.Availablefrom:http://www. ncbi.nlm.nih.gov/pmc/articles/PMC3250997. [Last accessed on March 07 2012]. 11. HonghuiC,TungYC,LiB,IqbalK,IqbalIG. Trophicfactorscounteractelevated EGF-2-inducedinhibitionofadult neurogenesis.NeurobiolAging2007 Aug;28(8):1148-62. 12. RubenJB,DafangWu,ManfredW.In Vivoupregulationofthebloodbrain barrierGLUT1glucosetransporterby brain-derivedpeptides.Neuroscience Research 1999;34:217-224. Citethisarticleas:JainN,YadavS,Goyal M,SingalKK,GuptaP,BansalM. Cerebroproteinhydrolysate:Innovation inNeurodegenerativedisorders.IntJ Med and Dent Sci 2014; 3(1):382-385. Source of Support: Nil Conflict of Interest: No
