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Objective Metformin has a potent inhibitory activity against inflammation and oxidative stress, which inevitably occur in sepsis-associated encephalopathy (SAE). The precise mechanisms underlying neuroprotective effects of metformin in SAE, are still unclear. In the present work, the protective effect of metformin on SAE using cecal ligation and puncture (CLP) model of sepsis, was assessed. Materials And Methods In this experimental study, CLP procedure was performed in Wistar rats and 50 mg/kg metformin was administered immediately. Specific markers of sepsis severity, inflammation, blood brain barrier (BBB) dysfunction, and brain injury, were investigated. Specific assay kits and real-time polymerase chain reaction (RT-PCR) were used. Histopathological assessment was also carried out. Results Treatment with metformin decreased murine sepsis score (MSS), lactate, platelet lymphocyte ratio (PLR), and high mobility group box (HMGB1) levels. The expression levels of claudin 3 (Cldn3) and claudin 5 (Cldn5) were increased following treatment with metformin. Metformin decreased the expression of S100b, neuron specific enolase (Nse), and glial fibrillary acidic protein (Gfap). Conclusion Our study suggests that metformin may inhibit inflammation and increase tight junction protein expressions which may improve BBB function and attenuate CLP-induced brain injury. Hence, the potential beneficial effects of metformin in sepsis, should be considered in future.

Cerebral infarction presents with neurological deficits caused by the death of neurons in a focal area of the brain. S100B is a biomarker that increases in brain damage. Neuroprotectives can reduce the brain sequels after neurological insult. The purpose of this study was to evaluate the neuroprotective effects of L-carnitine and Fat emulsion (Lipofundin®) alone and in combination in patients with ischemic stroke. In a prospective, RCT, and double-blind study 100 patients with MCA ischemic cerebrovascular accident who were admitted in the first 24 h of injury entered the study. The patients were randomly assigned into four groups of L-carnitine, fat emulsion, L-carnitine plus fat emulsion and control. Fat emulsion 10%, 500 mL, was infused over 6 to 12 h and 1 gr of L-carnitine (10 mL of solution) was administered orally to patients in addition to common therapies, according to the American Heart Association and American Stroke Association (AHA/ASA) guidelines. The patients in the control group received only the usual treatment according to stroke guidelines. Blood samples before the intervention, then after 24 h, 48 h, and 7 days later were taken and immunoenzymatic colorimetric method was used for quantitative determination of S100B concentration in the patients’ serum. In the within group analysis, all of our treatment interventions (except control group) have decreased S100B levels statistically significant (P < 0.05). Moreover, changes in observed levels of S100B before and after intervention were different between the groups and the observed differences were statistically significant (P = 0.01). In the GEE model, it was found that S100B levels in the L-carnitine plus fat emulsion group decreased more than the control group and this decline has been statistically significant [P = 0.02, 20.47 (CI 95%: 6.25-34.41)], but in comparison of L-carnitine and fat emulsion group with control group, did not reached statistical significance (P > 0.05). Based on the results obtained from this study, it seems that L-carnitine with fat emulsion could lead to neuroprotective effects with a significant reduction in the S100B biomarker.

Spinal cord injury is a devastating chronic condition resulting in temporary or permanent motor, sensory or autonomic dysfunction of the cord. The manifestation of spinal cord injury based on the severity and involved areas could be different. Numerous studies have demonstrated that bradycardia, hypotension, and orthostatic hypotension are present insignificant number of patients after spinal cord injury which peaks at 4th day of injury. Although vasopressors are common drugs that have been used to restore blood pressure and heart rate in patients with neurogenic shock, there is limited data regarding pharmacologic management of bradycardia and hypotension after spinal cord injury. Midodrine is a potent vasopressor approved for the management of symptomatic orthostatic hypotension. Theophylline and aminophylline are methylxanthine derivatives. There are very few case reports concerning the use of midodrine and methylxanthines for treatment of hypotension in patients with spinal cord injury. In this case report and review of the articles we report a 45 year old woman with a diagnosis of spinal cord injury who was successfully managed with midodrine and aminophylline and then we review current case reports. Based on our case report and other available data, midodrine as well as methylxanthines can be suggested as therapeutic options for managing symptoms in spinal cord injury patients.