Investigating the therapeutic effects of nimodipine on vasogenic cerebral edema and blood-brain barrier impairment in an ischemic stroke rat model.

Vasogenic brain edema, a potentially life-threatening consequence following an acute ischemic stroke, is a major clinical problem. This research aims to explore the therapeutic benefits of nimodipine, a calcium channel blocker, in mitigating vasogenic cerebral edema and preserving blood-brain barrier (BBB) function in an ischemic stroke rat model. In this research, animals underwent the induction of ischemic stroke via a 60-min blockage of the middle cerebral artery and treated with a nonhypotensive dose of nimodipine (1 mg/kg/day) for a duration of five days. The wet/dry method was employed to identify cerebral edema, and the Evans blue dye extravasation technique was used to assess the permeability of the BBB. Furthermore, immunofluorescence staining was utilized to assess the protein expression levels of matrix metalloproteinase-9 (MMP-9) and intercellular adhesion molecule-1 (ICAM-1). The study also examined mitochondrial function by evaluating mitochondrial swelling, succinate dehydrogenase (SDH) activity, the collapse of mitochondrial membrane potential (MMP), and the generation of reactive oxygen species (ROS). Post-stroke administration of nimodipine led to a significant decrease in cerebral edema and maintained the integrity of the BBB. The protective effects observed were associated with a reduction in cell apoptosis as well as decreased expression of MMP-9 and ICAM-1. Furthermore, nimodipine was observed to reduce mitochondrial swelling and ROS levels while simultaneously restoring MMP and SDH activity. These results suggest that nimodipine may reduce cerebral edema and BBB breakdown caused by ischemia/reperfusion. This effect is potentially mediated through the reduction of MMP-9 and ICAM-1 levels and the enhancement of mitochondrial function.

The Neuroprotective Effect of Mesna on Cisplatin-Induced Neurotoxicity: Behavioral, Electrophysiological, and Molecular Studies.

Peripheral neuropathy and cognitive impairments following cisplatin administration may interfere with the clinical usage of the drug. Mesna is a chemoprotective agent with anti-inflammatory and anti-oxidant effects. Our study aimed to investigate the protective effects of mesna against cisplatin-induced neurotoxicity. Neurotoxicity was induced by the administration of 2.5 mg/kg cisplatin twice a week for four consecutive weeks in male Wistar rats. The neuroprotective effect of mesna (150 mg/kg/day) was evaluated through behavioral, electrophysiological, and molecular studies. Cisplatin treatment caused passive avoidance memory impairment, increased anxiety-like behaviors, altered thermal sensitivity, and decreased muscle strength in a grip strength test. Our electrophysiological studies indicated that administration of cisplatin induced peripheral sensory neuropathy and decreased the amplitudes of the compound action potential of sensory nerves. Cisplatin administration increased MDA and 4-HNE levels and decreased anti-oxidant (SOD and GPx) enzymes. Proinflammatory cytokines (IL-1ß and TNF-α) and metalloproteinase-2 and 9 (MMP-2/9) were increased by cisplatin treatment. Morphological alterations were observed in the dorsal root ganglion (DRG) of cisplatin-treated rats. Cognitive impairments, anxiety, muscle strength, and thermal sensitivity changes induced by cisplatin were improved with mesna treatment. The reduced conduction velocity in sensory nerves was recovered in the cisplatin + mesna group. Mesna partially alleviated redox imbalance, reduced the proinflammatory cytokines, and MMP-2/9 levels. Mesna administration also relieved the morphological changes in DRG of cisplatin-treated rats. In conclusion, our results revealed that mesna can alleviate cisplatin-induced central and peripheral nervous system toxicity. These results support the concept that chemotherapy-induced neuropathy can be partially inhibited via mesna.

Calcitriol protects the Blood-Brain Barrier integrity against ischemic stroke and reduces vasogenic brain edema via antioxidant and antiapoptotic actions in rats.

BACKGROUND: Vasogenic brain edema is the most important complication of ischemic stroke that aggravates primary brain injury. Ischemia-Reperfusion (IR)-induced Blood-Brain Barrier (BBB) impairment limits the use of recombinant tissue plasminogen activator (r-tPA) by increasing the possibility of hemorrhagic transformation and contributing to vasogenic edema and neuroinflammation. This study examined the effects of post-ischemic treatment with calcitriol on cerebral infarction, vasogenic edema formation and BBB disruption in a rat model of ischemic stroke. METHODS: Male Sprague-Dawley rats were divided into three main groups, including the sham, IR + vehicle and IR + calcitriol groups. Transient focal cerebral ischemia was induced by a 60-min-long occlusion of the left middle cerebral artery. The infarct volume, brain edema, BBB permeability and antioxidant enzyme activities were evaluated 24 h after ischemia. Immunohistochemical analysis was conducted to investigate cell apoptosis and Brain-Derived Neurotrophic Factor (BDNF) protein expression five days after ischemia. RESULTS: Compared to the IR + vehicle group, the IR + calcitriol group showed a reduced brain infarction volume, attenuated brain edema formation and improved BBB function. These protective effects were followed by the upregulation of antioxidant enzyme activities in the brain tissue. Additionally, a diminished cell apoptosis and an increased BDNF immunoreactivity were obtained in the IR + calcitriol group. CONCLUSION: Calcitriol may reduce brain injury and attenuate vasogenic edema by upregulating antioxidant enzymes activities, reducing cell apoptosis and increasing BDNF protein in the brain tissue in a rat model of ischemic stroke.

Magnesium sulfate protects blood-brain barrier integrity and reduces brain edema after acute ischemic stroke in rats.

Brain edema is a fatal complication of acute ischemic stroke and associated with worse outcomes in patients. This study was designed to evaluate the effects of magnesium sulfate on vasogenic brain edema formation and blood-brain barrier (BBB) disruption caused by ischemia-reperfusion (IR) in a rat model of ischemic stroke. A total of 72 male Sprague-Dawley rats were categorized into the following three primary groups: sham, control ischemic, magnesium-sulfate-treated (300 mg/kg loading dose, followed by an additional 100 mg/kg) ischemic (n = 24 in each group). Transient focal cerebral ischemia was induced by 60-min-long occlusion of the left middle cerebral artery, followed by 24-h-long reperfusion. Sensorimotor deficits, infarct volume, and brain edema were evaluated at the end of the reperfusion period. The BBB permeability was assessed by Evans Blue extravasation technique. Lipid peroxidation levels were assessed by measuring the malondialdehyde content in the brain tissue homogenate, and the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase were detected according to the technical manual of the assay kits. Induction of cerebral ischemia in the control group produced considerable BBB damage in conjunction with severe brain edema formation. Treatment with magnesium sulfate significantly attenuated brain edema and protected BBB integrity in the ischemic lesioned hemisphere. In addition, magnesium sulfate reduced lipid peroxidation and increased antioxidant protection of brain tissue by upregulating the activities of antioxidant enzymes. Treatment with magnesium sulfate protected BBB integrity against IR-induced damage and reduced vasogenic edema formation partly via antioxidant mechanisms in a rat model of acute ischemic stroke.