| Recently, there is a great progress in the study of ischemia cerebral vascular disease(1CVD) , the age of drug combination is coming, combinative treatment of aiming at cerebral vascular and cell during the ischemic injury may have a great influence on the stroke prognose. Earlier period thrombolysis is a therapy about vascular, since the use of r - tPA was accepted by FDA in 1996, thrombolysis has ever been the hot study. With the development of thrombolysis in ICVD, the reperfusion injury has been thought highly of increasingly after the cerebral blood flow was restored. Animal experiments have proved that protection of nerve cell may increased the therapeutic time window of successful reperfusion, while neuroprotection would be the first tragedy if the reperfusion injury once occurred, neuroprotection can act various links on "ischemic injury cascade reaction" and block different mechanisms of cell necrosis after ischemia and reperfusion. As a multi - effective neurotrophic factor , Glial cell line - derived neurotrophic factor (GDNF) can treat not only neurodegeneration disease but also cerebral ischemic injury. Here we first discuss the therapeutic time window(TTW)of GDNF on cerebral ischemic and reperfusion injury, so that we can provide the clinic with a new neuroprotective medicine and its TTW.MethodsI . Animals and groupRats were divided into two groups; infarct volumn group( V) and immunohistochemistry group(I). the former then was divided into saline group (Nv n = 5 ) , GDNF group ( Gv n = 15 ) which was divided into Oh group( Gv0n= 5 ) .Jh group( GV1 n = 5 ) ,3h group( GV3 n = 5 ) according to the administration time; the latter was divided into sham group(S n = 3 ) , saline group( N1 n = 5 ) , Oh group( Gv0n = 5 ) and 3h group(Gv3 n=5).II. Instruments and Reagents; SN - 2 type brain solid positioner (shanghai) ; Metamorph microimage analytical system (Japan) ;GDNF ( Shenzhen Jingmei Company) ; Caspase - 3 and TNF - apolyclonal antibody (Wuhan Boshide Company).III. MCAO and administrationThe transisent right middle cerebral artery occlusion was made on the basis of Zea - Longa method, all rats were treated by brain surface administration.IV. Observation and measure methodsInfarct volumn was calculated by TTCstaining at 24h after ischemia; the cell form was observed by HEstaining; using imminohisto-chemistry method observe the expression of Caspase - 3 and TNF -aprotein at 12h after ischemia in penumbra.ResultsI . Light microscopyTreatment with GDNF markedly lightened the ischemic changes of frontal and parietal lobe as compared to control group.II. Infarct volumn comparisionAs compared to Nv group, the infarct volumn was significantly reduced at Gv0 group( P < 0. 01) ; so was at GV1 group ( p < 0. 05 ) , but became insignificant at Gv3 group ( p > 0.05).III. Infarct area comparisionAs compared to Nv group, the infarct areas of 2,3,4 layer were reduced at Gv0 group and GV1 group( p <0. 05) , but became insignificant at Gv3 group( p >0. 05).IV. Grave value comparisionThere is no expression of Caspase - 3 and TNF - aprotein in S group. Many positive cells expressing Caspase -3 and TNF - aprotein were shown in N, group at the cortex of frontal and parietal lobe in ischemic side, but showed significant reduction in Gv0 group (p <0. 05) and showed no reduction in Gv3 group( p > 0.05). Both the expression of TNF - aprotein in Gv0 group and in GV3 group had no marked difference.DiscussionThe reperfusion injury reached more 70% during the whole ischemic injury, penumbra is the main region of reperfusion injury, so is the region of neuroprotective intervention, which is important in the therapy of acute ischemic stroke. According to past study, the cortex of frontal and parietal lobe in ischemic side may be thought of penumbra.Now the reperfusion injury may derived from two lines, the one iscell apoptosis, the other is inflammatory reaction. Aming directly at the two pathologic and physiologic mechanism, many neuroprotective medi...
|
PDF Full Text Request