| Background and ObjectiveCerebral hemorrhage is a serious hazard to human health, higher morbidity lethaldisease, the incidence of11-37/10million annually, accounting for6%-17%of allstrokes,30-day mortality was38%-54%, the majority of surviving by varying degreesof residual loss of nerve function. Due to the complexity of the organizational structureof the brain and brain hemorrhage caused by brain damage is through a variety ofmechanisms, hematoma and conventional treatment alone is difficult to achieve thedesired effect of neurological rehabilitation. Finding effective ways to treat, tominimize mortality and improve cerebral hemorrhage after neurological recovery is theproblem we need deal with.A lot of nerve damage after cerebral hemorrhage, neural pathway is the pathologicalbasis of cerebral hemorrhage injury, once neuronal injury often leads to permanent lossof function, so how to effectively control the local inflammatory response and reduceirreversible neuronal damage, promote nerve regeneration, is the treatment ofhemorrhagic brain injury urgent problem.Now, with the large number of applications in the treatment of nutritional factors in avariety of disciplines, and get a lot of basic research in diseases such as cerebralhemorrhage, and gained rapid progress. These have made great progress on the pace of its shift to a clinical application.Brain-derived neurotrophic factor (brain derived neurotrophic factor, BDNF) is oneof the most important neurotrophic factors, can promote neuronal regeneration and theformation of synaptic connections in the central nervous system and so on. In in vitroexperiments, BDNF promotes ependymal layer of nerve cells and cortical area underneuronal survival. In vivo, BDNF can promote cerebral ischemia, traumatic braininjury, and toxic brain injury in neuronal survival. In the rat model of cerebralischemia, Wolf-Rüdiger Sch bitz etc. BDNF30minutes after intravenous injection incerebral cortex have found reduced infarct size. Viorica Pencea etintracerebroventricular injection BDNF, found to significantly increase neuronalproliferation and promote cell survival and differentiation of neural progenitor cells.In the rat model of cerebral hemorrhage, hematoma was found BDNF have reducedvolume of tissue damage area and promote nerve regeneration. The study found,BDNF can make ERK1/2and Akt phosphorylation regulation mesons were activatedRAS/MAPK pathway and PI3K/Akt ways to achieve neuroprotection, by upregulatingthe expression of Bcl-2family proteins, Bax down realization of anti-neuronalexpression of apoptosis. Our previous studies verify the collagen-binding domain(CBD) combined with BDNF promote nerve regeneration in rats with ischemic braindamage in neuronal apoptosis and anti-angiogenesis has made good effect.Since the blood-brain barrier to protect brain tissue, the traditional intravenous drugcan not be safely and effectively to the brain play a role in the injury site, the use ofviruses, liposomes, chitosan drug carriers that can transport drugs into the cranialcavity, but there security and poor targeting still have many problems. Directed targetedtherapy for drug delivery and reduce drug side effects brought hopes. However, theability to find specific targets for targeted therapy is the key to solve the problem in thearea if there is damage to the brain hemorrhage specifically targeted sites? Can we finda combination of this target biological material security, sustained slow release of thedrug? These results not only provide a theoretical basis for the relationship to drug targeting and treatment of cerebral hemorrhage clinical application of new materialstargeted therapy.CBD (collagen-bingding domain) polypeptide structure, collagen-binding domain isthe study of people discovered the site of action of collagenase. Polymerase chainreaction (PCR) technology, the CBD-BDNF gene amplification, insert the pET-28avector, and transfected into E.coli, so E.coli protein expression in the neural basis ofnutritional factors on the structure of collagen in a structural modification of peptidebinding region, the formation of CBD-BDNF. BDNF can fixed on collagen surface,thus forming sustained release systems. Experiments show that there CBD neurotrophicfactor polypeptides repair of nerve damage is far better than ordinary neurotrophicfactor.In the subependymal zone of rats, the distribution of a large number of type Icollagen, and subependymal zone (subventricularzone, SVZ) of endogenous neuralprogenitor cells, the main local proliferation. Therefore, the purpose of this paper is tostudy the subependymal zone targeting collagen BDNF treatment of intracerebralhemorrhagic stroke transplant effect, explore CBD-BDNF treatment of hemorrhagicstroke can be combined with subependymal zone, at the time the formation of sustainedrelease system, more long duration in space, more direct proliferation of endogenousneural progenitor cells stimulated ependymal zone, thereby promoting recovery afterintracerebral hemorrhage injury for the treatment of hemorrhagic nutritional factors theclinical application of stroke to provide adequate theoretical basis.MethodsIntends to establish ICH rat model to study the role of collagen after ICH injurytargeting BDNF. The main content of the research are as follows: Injecting into Ⅳcollagenase by stereotactic injection method to position caudate nucleus, making ratmodel of cerebral hemorrhage were randomly divided into groups of phosphate buffer(PBS group), BDNF treatment group. In the lateral ventricle were injected10ul (0.5nmol) NAT-BDNF,10ul (0.5nmol) CBD-BDNF,10ul (0.5nmol) PBS. After2weeksof treatment, the three groups were performed zoology score, immunohistochemicalstaining, Micro-PET, nano-SPECT,7.0T MRI scans to evaluate the effectiveness ofCBD-BDNF treatment of intracerebral hemorrhage injury in rats and the possiblemechanism.Results1.CBD binding region significantly improve the role of BDNF on damage repair.CBD-BDNF treatment groups neurological recovery than NAT-BDNF group and PBSgroup, cell proliferation in the subependymal zone active. The number of survivingneurons and the number of new blood vessels bleeding CBD-BDNF treatment groupwas significantly more than the surrounding area phosphate buffer group.2.Micor-PET showed increased brain hemorrhage side of metabolic activity. SPECT/CT perfusion imaging showed partial damage to the side of intracerebral hemorrhagewas significantly reduced perfusion deletion region. MRI imaging showed the volumeof CBD-BDNF treatment group hematoma after intracerebral hemorrhage injury issignificantly less than NAT-BDNF and PBS groups. And by functional magneticresonance imaging fMRI assessment can be found in neurons CBD-BDNF treatmentgroup regeneration and recovery better than NAT-BDNF and PBS groups. Finally, themeasurement can be derived by T2WI, the extent of tissue damage CBD-BDNFtreatment group was significantly less than the NAT-BDNF and PBS groups.3. BDNF can inhance the function of the brain injury in SD rats; raised newbornneurons (PCNA), the expression of glial cells (GFAP), mature neurons (Neun) and otherproteins, reducing neuronal apoptosis may be one of the main mechanisms.Conclusion1.CBD-BDNF was injected SVZ region can significantly improve recovery after brainfunction in SD rats after ICH, promote the proliferation of SVZ-derived neural progenitor cells in the region, differentiation of neurons have a protective effect,improving newborn the density of blood vessels, inhibit neuronal apoptosis.2.7.0T MRI can be fast, accurate and non-invasive in vivo evaluation of the state ofbrain damage after cerebral hemorrhage animal model organizational structure, thedegree of tissue edema, changes in neuronal metabolites, to evaluate and guidetreatment decisions provide strong after cerebral hemorrhage basis. |
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