Experimental Studies Of Neuroprotection Combined Antiapoptosis Therapy

Neuroprotection is the traditional method to protect neurons, there are many kinds of neuroprotective agent However, there is no neuroprotective agent passed through the test of U.S.A II clinic experiment up to present, it is doubtful of some clinic protective therapy. It becomes important to improve therapeutic effect and extend therapeutic time window (TTW) in clinic. We think one of the most difficult problems is the block of brain-blood barrier (BBB). The cerebral spinal fluid (CSF) belong to the extracellular fluid of neurons, so it may be a potential way of administration. Neurons were damaged easily under condition of the ischemia, it will be death after 6h ischemia commonly. It may be a good method to treat cerebral ischemia and extend the therapeutic time window(TTW) that combined different neuroprotective agent and antiapoptosis.Materals and methods1. we studied the effect of NGF in different administration way of inject cerebral ventricle (i.c.v )and inject peritoneal (i.p), the TTC method was used to estimate the volume of infarct, the models were focal ischemic of rats by string-steming arteria cerebral media.2. NGF was combined with MK-801 to treat cerebral ischemia by two different ways. The forebrain infarct volume was estimated by TTC method.3. In the condition of combined NGF and MK-801, the Casepase-1 was also combined to treat cerebral ischemia.4. The character of cerebral ischemia before and after treatment were observed by electron microscope.5. Clinic test, the Citicoline was used to treat cerebral ischemia patients.6. The side effect of the method of administration by CSF was observed by HE pathological slice.Results1. The neuroprotective effect of NGF was improved obviously by administration through CSF.2. The neuroprotective effect will be enhenced while NGF and MK-801 were combined administration by i.c.v.3. The TTW was extended in some degree when NGF combined with MK-801and Casepase-1 inhibitor by icv administration.4. Apoptosis appeared after ischemia 6h, and enhanced gradually.5. In clinic, the neuroprotective effect will be enhenced while the neuroprotective agent was used by CSF.6. There were no side effect on cerebral-spinal membrane while NGF administration by CSF.Conclusions1. It was the best way of administration neuroprotective agents by CSF.2. The neuroprotective effect will be enhenced while administration by CSF.3. In some degree, the TTW will be extended while combined different neuroprotective agents and antiapoptosis.4. There was little apoptosis in the early of ischemia, the effect of antiapoptosis did not confirm. After 6h of ischemia, antiapoptosis was effective and apoptosis happened in all around ischemia certer.5. It would be used to clinic administration by CSF.