Fenofibrate protects the neurovascular unit and ameliorates plasma corticosterone levels in pentylenetetrazole-induced kindling seizure in mice.

Epileptic seizures are the most common neurological diseases that change the function of neurovascular unit at molecular levels accompanied by activation of a wide variety of neurodegenerative cascades. Based on the pleiotropic functions of peroxisome proliferator-activated receptor-alpha (PPARα), the current study evaluated the neuroprotective effects of fenofibrate (an effective PPARα agonist) on the brain injuries induced by pentylenetetrazole (PTZ)-induced kindling seizure. Adult male NMRI mice were randomly assigned into four groups (n = 14) as follows; control, untreated kindled mice (PTZ) and two fenofibrate-treated kindled groups. Repeated intraperitoneal injections of PTZ (45 mg/kg) were used to develop kindling seizure every 48 h for 21 days. Treated mice were administered orally fenofibrate at doses of 30 and 50 mg/kg/day during the study. Plasma corticosterone and brain levels of brain-derived neurotrophic factor (BDNF), malondialdehyde (MDA) and mRNA transcription of p53, as well as blood-brain barrier (BBB) permeability, were determined at termination of the study. Fenofibrate considerably improved seizure latency and anxiety-like behaviors in treated kindled mice. Fenofibrate at doses of 30 and 50 mg/kg significantly (P < 0.001) decreased plasma corticosterone (56.88 ± 0.80 and 54.81 ± 0.29 ng/mL, respectively) compared to PTZ group (74.96 ± 1.60 ng/mL). It also significantly (P < 0.05) decreased BDNF levels in both treatment groups (8.13 ± 0.14 and 8.74 ± 0.09 ng/mL, respectively) compared to PTZ group (9.68 ± 0.20 ng/mL). Fenofibrate particularly at higher dose significantly (P < 0.01) decreased MDA content and mRNA expression levels of p53 in treated kindled mice by 67% and 28%, respectively, compared to PTZ group. Similarly, 50 mg/kg fenofibrate significantly (P < 0.05) decreased Evans blue extravasation into brain in treated kindled mice (8.72 ± 0.96 µg/g) compared to PTZ group (15.31 ± 2.18 µg/g). Our results revealed the anticonvulsive and neuroprotective effects of fenofibrate in PTZ-induced kindling seizure in mice. Fenofibrate also improved the neurovascular functions at molecular levels in kindling seizure that might be associated with ameliorating the seizure behaviors.

Fullerenol nanoparticles decrease ischaemia-induced brain injury and oedema through inhibition of oxidative damage and aquaporin-1 expression in ischaemic stroke.

BACKGROUND: We examined the possible protective effects of fullerenol nanoparticles on brain injuries and oedema in experimental model of ischaemic stroke through inhibition of oxidative damage and aquaporin-1 (AQP-1) expression. METHODS: Experiment was done in three groups of rats (N = 66): sham, control ischaemia and ischaemic treatment. Ischaemia was induced by 90-minutes middle cerebral artery occlusion (MCAO) followed by 24 hours of reperfusion. Rats received a dose of 10 mg/kg of fullerenol 30 minutes before MCAO. Infarction, brain oedema, malondialdehyde (MDA) and nitrate contents as well as mRNA level of AQP-1 were determined 24 hours after termination of MCAO. RESULTS: Administration of fullerenol before MCAO significantly reduced the infarction of cortex and striatum by 72 and 77%, respectively. MCAO induced brain oedema in control ischaemic rats (3.83 ± 0.53%), whereas, fullerenol significantly reduced it (0.91 ± 0.55%). The contents of MDA and nitrate increased in ischaemic hemispheres by 86 and 41%, respectively. Fullerenol considerably reduced the MDA and nitrate contents by 83 and 48%, respectively. Moreover, MCAO noticeably increased the mRNA level of AQP-1 in ischaemic hemispheres by 22%, whereas fullerenol significantly decreased it by 29%. DISCUSSION: Fullerenol is able to reduce ischaemia-induced brain injuries and oedema possibly through inhibition of oxidative damage and AQP-1 expression in ischaemic stroke.