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
