INTRANASAL DELIVERY OF NERVE GROWTH FACTOR TO PROTECT THE CENTRAL NERVOUS SYSTEM AGAINST ACUTE CEREBRAL INFARCTION

Objective To confirmed reliability and feasibility of intranasal nerve growth factor (NGF) bypassing the blood-brain barrier and its potential neuroprotective effects on acute cerebral ischemia. Methods (1) To assay NGF concentrations in different brain regions after middle cerebral artery occlusion (MCAO).Rats were randomly divided into intranasal (IN) NGF, intravenous (IV) NGF, and untreated group (n= 4). The concentra-tions of NGF of different brain regions in the three groups after MCAO were measured by ELISA. (2) To observe neuro-protective action of NGF on focal cerebral ischemic damage. Rats were randomly assigned to 4 groups: IN vehicle, IN NGF, IV vehicle, IV NGF (n= 8). Treatment was initiated 30 minutes after onset of MCAO and given again 24 hours later. Three neurologic behavioral tests were performed 24 and 48 hours following onset of MCAO. Corrected infarct volumes were determined 48 hours after onset of MCAO. Results The olfactory bulb in IN NGF group obtained the highest concentration (3252 pg/g) of NGF among all regions, followed by the hippocampus. The NGF concentrations in the olfactory bulb and hippocampus in IN NGF group were markedly higher than that in IV NGF and control groups. The infarct volume in IN NGF group was markedly reduced by 38.8% compared with IN vehicle group. IN NGF group vestibulum function markedly improved compared with IN vehicle group at 24 and 48 hours after onset of MCAO (P 24 h = 0.02 and P 48 h = 0.04, respectively). Conclusion Intranasal NGF could pass through the blood-brain barrier, reach the central nervous system, reduce infarct volume, and improve neurologic function in rats following MCAO. Intranasal delivery of NGF may be a promising treat-ment for stroke.

ANALYSIS OF RISK FACTORS IN 3901 PATIENTS WITH STROKE

Objective To estimate the frequency of various risk factors for overall stroke and to identify risk factors for cerebral infarction (CI) versus intracerebral hemorrhage (ICH) in a large hospital-based stroke registry. Methods Data from a total of 3901 patients, consisting of 3525 patients with CI and 376 patients with ICH were pros-pectively coded and entered into a computerized data bank. Results Hypertension and smoking were the most prominent factors affecting overall stroke followed by mild internal carotid artery stenosis (< 50%), hypercholesterolemia, transient ischemic attacks (TIAs), diabetes mellitus, and cardiac ischemia. Univariate analysis showed that factors in male significantly associated with CI versus ICH were old age, a family history of stroke, and intermittent claudication; whereas in female the factors were oral contraception and migraine. By multivariate analysis, in all patients, the factors significantly associated with CI as opposed to ICH were smoking, hyperch-olesterolemia, migraine, TIAs, atrial fibrillation, structural heart disease, and arterial disease. Hypertension was the only significant factor related with ICH versus CI.Conclusions The factors for ischemic and hemorrhagic stroke are not exactly the same. Cardiac and arterial disease are the most powerful factors associated with CI rather than ICH.