Erythropoietin prevents the increase in blood-brain barrier permeability during pentylentetrazol induced seizures.

Recombinant human erythropoietin (r-Hu EPO) has been shown to exert neuroprotection in ischemic, excitotoxicity, trauma, convulsions and neurodegenerative disorders. Blood-brain barrier (BBB) leakage plays a role in the pathogenesis of many pathological states of the brain including neurodegenerative disorders. This study aimed to investigate the effects of r-Hu EPO on BBB integrity in pentylentetrazol (PTZ) induced seizures in rats. Seizures were observed and evaluated regard to latency and intensity for an hour. Macroscopical and spectrophotometrical measurement of Evans Blue (EB) leakage were observed for BBB integrity. r-Hu EPO was given intraperitoneally 24 h prior to seizure induction. Total seizure duration of 720+/-50 s after single PTZ administration (80 mg/kg i.p.) was declined to 190+/-40 s in r-Hu EPO pretreatment. A typical BBB breakdown pattern (i.e. staining in cerebellum, cerebral cortex, midbrain, hippocampus, thalamus and corpus striatum) was observed in rat brains with PTZ induced seizures; whereas, EPO pretreatment confined BBB leakage to cerebellum and cortical areas, and lessened the intensity of tonic-clonic seizures observed in PTZ seizures. The protective effect of r-Hu EPO on BBB permeability in seizures is a new and original finding. The protective action of r-Hu EPO in seizures and some of CNS pathologies warrant further investigations.

Protection of blood-brain barrier breakdown by nifedipine in adrenaline-induced acute hypertension.

The question of whether influxes of ionic Ca+2 into cerebral endothelium plays an important role in increased vascular permeability consequent to an acute hypertension is not accurately resolved. We tested the effect of nifedipine, a calcium entry blocker, on the cerebrovascular permeability for proteins in adrenalin-induced acute hypertension. The experiments were carried out on male Wistar rats. The experimental groups consisted of normotensive saline controls, adrenaline-induced hypertensive rats, and adrenalin-induced hypertensive rats as pre-treated or post-treated with a bolus of nifedipine. Brains of hypertensive rats showed increased permeability to Evans Blue-Albumin complex, when blood pressure elevated rapidly to more than 170 mmHg. The number and size of areas of Evans-Blue extravasation were smaller if an increase in blood pressure was prevented. The short lasting elevation of blood pressure did not result in protein extravasation in brains of hypertensive rats. The results suggest that nifedipine can modify the permeability disruptions observed in acutely hypertensive rats. The data also support the hypothesis that Ca+2 may be responsible for the changes in permeability of BBB in hypertension by mediating the contraction of vascular muscles.