Topiramate attenuates early brain injury following subarachnoid haemorrhage in rats via duplex protection against inflammation and neuronal cell death.

摘要: Abstract Early brain injury (EBI) following aneurysmal subarachnoid haemorrhage (SAH) insults contributes to the poor prognosis and high mortality observed in SAH patients. Topiramate (TPM) is a novel, broad-spectrum, antiepileptic drug with reported protective effect against several injuries. The current study aimed investigate potential of TPM for neuroprotection EBI after possible dose-dependency this effect. An endovascular perforation model was established rats, administered by intraperitoneal injection surgery at three different doses (20 mg/kg, 40 mg/kg, 80 mg/kg). animals’ neurological scores water content were evaluated, ELISA, Western blotting immunostaining assays conducted assess TPM. results revealed that lowers elevated levels myeloperoxidase proinflammatory mediators dose-related fashion, nuclear factor-kappa B (NF-κB) signalling pathway target neuroinflammation regulation. In addition, ameliorated SAH-induced cortical neuronal apoptosis influencing Bax, Bcl-2 cleaved caspase-3 protein expression, enhanced dose-dependent manner. Various dosages also upregulated expression γ-aminobutyric acid (GABA)-ergic molecules, GABAA receptor (GABAAR) α1, GABAAR γ2, K+–Cl− co-transporter 2 (KCC2) together downregulated Na+–K+–Cl− 1 (NKCC1) expression. Thus, may be an effective neuroprotectant regulating cell death.