Concomitant Guillain-Barré Syndrome and COVID-19: A Meta-Analysis of Cases.

Background and Objectives: Recent findings demonstrate that the transmigration of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) to the nervous system implicates severe neurotropic pathologies, including the onset of the rare disease called Guillain-Barré syndrome (GBS) which is characterized by immune-mediated polyneuropathy. This study aimed to identify the predisposing factors and the clinical features of coronavirus disease 2019 (COVID-19)-induced GBS. Materials and Methods: We have performed an analysis of 147 cases. A systematic review of the published research work was performed per the PRISMA statement to obtain individual participant data (IPD) for the meta-analysis. The search was conducted through PubMed, using the combined search terms "Guillain-Barré syndrome" and "COVID-19". All case reports and series in the English language with accessed full text were included in the search. Results: A systematic database search led to the retrieval of 112 peer-reviewed articles published between 1 April 2020, and 8 February 2022. The articles comprised 16 case series and 96 case reports containing IPD for 147 patients. Our findings showed that 77.6% of all cases were 40 years or older. Males comprised most of the cases (65.3%; n = 96). The intensive care unit (ICU) admission was 44.9%, and the need for mechanical ventilation (MV) was 38.1%. The patients presented with hyporeflexia or areflexia (84.4%; n = 124), lower limb strength and sensation impairment (93.2%; n = 138), upper limb strength and sensation impairment (85.7; n = 126), and somatic sensation impairment (72.8%; n = 107). The patients presented with increased cerebral spinal fluid (CSF) protein levels (92%; n = 92) and the presence of CSF albuminocytological dissociation (83.5%; n = 71). The most common variant of GBS observed was acute inflammatory demyelinating polyneuropathy (AIDP). We found that predisposing factors concomitant with COVID-19 and GBS were male gender and older age. Among the cases, patient mortality was 10.9%. Conclusions: A gap of knowledge exists regarding the complete spectrum of clinical characteristics of COVID-19-related GBS. Recent findings suggest that SARS-CoV-2 triggers GBS, as it follows a similar para-infectious pattern as the other viral agents contributing to the onset of GBS.

Limiting feeding to the active phase reduces blood pressure without the necessity of caloric reduction or fat mass loss.

Reducing body weight has been shown to lower blood pressure in obesity-related hypertension. However, success of those lifestyle interventions is limited due to poor long-term compliance. Emerging evidence indicates that feeding schedule plays a role on the regulation of blood pressure. With two studies, we examined the role of feeding schedule on energy homeostasis and blood pressure. In study 1, rats were fed a high-fat diet (HFD) ad libitum for 24 h (Control) or for 12 h during the dark phase (time-restricted feeding, TRF). In study 2, rats fed a HFD were administered a long-acting α-MSH analog at either light onset [melanotan II (MTII) light] or dark onset (MTII dark) or saline (Control). MTII light animals ate most of their calories during the active phase, similar to the TRF group. In study 1, Control and TRF rats consumed the same amount of food and gained the same amount of weight and fat mass. Interestingly, systolic and mean arterial pressure (MAP) was lower in the TRF group. In study 2, food intake was significantly lower in both MTII groups relative to Control. Although timing of injection affected light versus dark phase food consumption, neither body weight nor fat mass differed between MTII groups. Consistent with study 1, rats consuming their calories during the active phase displayed lower MAP. These data indicate that limiting feeding to the active phase reduces blood pressure without the necessity of reducing calories or fat mass, which could be relevant to obesity-related hypertension.

The effect of solifenacin on postvoid dribbling in women: results of a randomized, double-blind placebo-controlled trial.

INTRODUCTION AND HYPOTHESIS: To determine the effectiveness of the muscarinic receptor antagonist solifenacin (VESIcare®) in the treatment of postvoid dribbling (PVD). METHODS: We carried out a multicenter, 12-week, double-blind, randomized, placebo-controlled, parallel design study. Between 2012 and 2015, a total of 118 women (age 18-89 years) with PVD at least twice/weekly, were randomized to receive solifenacin (5 mg; n = 58) or placebo (n = 60) once daily. The primary outcome was the percentage reduction in PVD episodes. Secondary outcomes included the percentage of patients with ≥50% reduction in PVD episodes and changes in quality of life. RESULTS: There were no differences in either the primary or secondary outcome variables. Subgroup analysis, based on those with more severe disease (>10 PVD episodes/week), showed a greater and significant percentage reduction in the frequency of PVD episodes per day (60.3% vs 32.1%; p = 0.035) and a higher percentage of patients showing ≥50% reduction in the frequency of PVD episodes with solifenacin (68.1% vs 45.8%; p = 0.0476). A significant solifenacin effect occurred at week 2 and continued through week 12 for the subgroup. For solifenacin, PVD reduction was the same for the entire cohort and subgroup, whereas for placebo, it was 10% lower in the subgroup, declining from 42% to 32%. CONCLUSION: There were no differences in PVD outcomes between the solifenacin and placebo groups. Solifenacin may play a role in treating women with the most severe symptoms. Because of the powerful placebo response seen in this study, behavior-based interventions may be useful for treating PVD.

The Clinical Significance of Relative Bradycardia.

INTRODUCTION: Relative bradycardia is a poorly understood paradoxical phenomenon that refers to a clinical sign whereby the pulse rate is lower than expected for a given body temperature. OBJECTIVE: To provide an overview and describe infectious and noninfectious causes of relative bradycardia. METHODS: PubMed and Medline databases were searched using individual and Medical Subject Headings terms including relative bradycardia, fever, pulse-temperature dissociation and pulsetemperature deficit in human studies published from inception to October 2, 2016. The causes and incidence of relative bradycardia were reviewed. RESULTS: Relative bradycardia is found in a wide variety of infectious and noninfectious diseases. The pathogenesis remains poorly understood with proposed mechanisms including release of inflammatory cytokines, increased vagal tone, direct pathogenic effect on the myocardium, and electrolyte abnormalities. The incidence of this sign varies widely, which may be attributable to multiple factors, including population size, time course for measuring pulse and temperature, and lack of a consistent definition used. The fact that this sign is not consistently identified in case series suggests that relative bradycardia is caused by mechanisms presumably involving or influenced by pathogen and host factors. CONCLUSIONS: Relative bradycardia is a sensitive but nonspecific clinical sign that may be an important bedside tool for narrowing the differential diagnosis of potential infectious and noninfectious etiologies. Recognizing this relationship may assist the clinician by providing bedside clinical clues into potential etiologies of disease, particularly in the setting of infectious diseases and in circumstances when other stigma of disease is absent.

Factors associated with participation and completion of a survey-based study.

PURPOSE: The Healthy Work Place (HWP) study investigated methods to improve clinicians' dissatisfaction and burnout. The purpose of this paper is to identify factors that influenced study enrollment and completion and assess effects of initial clinic site enrollment rates on clinician outcomes, including satisfaction, burnout, stress and intent to leave practice. DESIGN/METHODOLOGY/APPROACH: In total, 144 primary care clinicians (general internists, family physicians, nurse practitioners and physician assistants) at 14 primary care clinics were analyzed. FINDINGS: In total, 72 clinicians enrolled in the study and completed the first survey (50 percent enrollment rate). Of these, 10 did not complete the second survey (86 percent completion rate). Gender, type, burnout, stress and intervention did not significantly affect survey completion. Hence, widespread agreement about most moral/ethical issues (72 percent vs 22 percent; p=0.0060) and general agreement on treatment methods (81 percent vs 50 percent; p=0.0490) were reported by providers that completed both surveys as opposed to just the initial survey. Providers with high initial clinic site enrollment rates (=50 percent providers) obtained better outcomes, including improvements in or no worsening of satisfaction (odds ratio (OR)=19.16; p=0.0217) and burnout (OR=6.24; p=0.0418). SOCIAL IMPLICATIONS: More providers experiencing workplace agreement completed the initial and final surveys, and providers at sites with higher initial enrollment rates obtained better outcomes including a higher rate of improvement or no worsening of job satisfaction and burnout. ORIGINALITY/VALUE: There is limited research on clinicians' workplace and other factors that influence their participation in survey-based studies. The findings help us to understand how these factors may affect quality of data collecting and outcome. Thus, the study provides us insight for improvement of quality in primary care.

Functional and structural changes of the urinary bladder following spinal cord injury; treatment with alpha lipoic acid.

BACKGROUND & AIM: Alpha lipoic acid (LA) was shown to exert neuroprotection in trauma-induced spinal cord injury (SCI), which is frequently associated with urinary bladder complaints in patients with SCI. Accordingly, the protective effects of LA on biochemical and histological changes in bladder as well as functional studies were assessed. METHODS: Wistar albino rats were divided as control, SCI, and LA (50 mg/kg/day, ip) treated SCI groups (SCI+LA). The standard weight-drop (100 g/cm force at T10) method was used to induce a moderately severe SCI. One week after the injury, neurological examination was performed and the rats were decapitated. Bladder samples were taken for histological examination, functional (isolated tissue bath) studies, and for the measurement of biochemical parameters (malondialdehyde, MDA; gluthathione, GSH; nerve growth factor, NGF; caspase-3, luminol and lucigenin chemiluminescences). RESULTS: SCI caused a significant (P < 0.001) increase in the detrusor muscle thickness. It increased the contractility responses to carbachol and relaxation responses to papaverine (P < 0.05-0.001). There were also significant alterations in MDA, caspase-3, luminol, and lucigenin chemiluminescences with concomitant decreases in NGF and GSH (P < 0.05). LA treatment reversed histological and functional (contraction and relaxation responses) changes induced by SCI (P < 0.05-0.001), but no significant recovery was observed in the impaired neurological functions. CONCLUSION: These results indicate that LA have a beneficial effect in improving the bladder tonus via its antioxidant and anti-inflammatory actions following SCI.

A systematic review of mobility/immobility in thromboembolism risk assessment models for hospitalized patients.

Hospitalized patients are at risk of venous thromboembolism (VTE) and prophylaxis is often suboptimal due to difficulty in identifying at-risk patients. Simple and validated risk-assessment models (RAMs) are available to assist clinicians in identifying patients who have a high risk for developing VTE. Despite the well-documented association of immobility with increased risk of thrombosis, immobility is not consistently defined in clinical studies. We conducted a systematic review of published VTE RAMs and used objective criteria to determine how the term immobility is defined in RAMs. We identified 17 RAMs with six being externally validated. The concept of immobility is vaguely described in different RAMs, impacting the validity of these models in clinical practice. The wide variability in defining mobility in RAMs precluded its accurate clinical application, further limiting generalization of published RAMs. Externally validated RAMs with clearly defined qualitative or quantitative terms of immobility are needed to assess VTE risk in real-time at the point-of-care.

Anorexic response to rapamycin does not appear to involve a central mechanism.

The authors have previously demonstrated that a low and intermittent peripheral dose of rapamycin (1 mg/kg three times/week) to rats inhibited mTORC1 signalling, but avoided the hyperlipidemia and diabetes-like syndrome associated with higher doses of rapamycin. The dosing regimen reduced food intake, body weight, adiposity, serum leptin and triglycerides. mTORC1 signalling was inhibited in both liver and hypothalamus, suggesting some of the actions, in particular the decrease in food intake, may be the results of a central mechanism. To test this hypothesis, rapamycin (30 µg/day for 4 weeks) was infused into 23-25-month-old F344xBN rats by intracerebroventricular (icv) mini pumps. Our results demonstrated that central infusion did not alter food intake or body weight, although there was a tendency for a decrease in body weight towards the end of the study. mTORC1 signalling, evidenced by decreased phosphorylation of S6 protein at end of 4 weeks, was not activated in liver, hypothalamus or hindbrain. Fat and lean mass, sum of white adipose tissues, brown adipose tissue, serum glucose, insulin and leptin levels remained unchanged. Thus, these data suggest that the anorexic and body weight responses evident with peripheral rapamycin are not the result of direct central action. The tendency for decreased body weight towards the end of study, suggests that there is either a slow transport of centrally administered rapamycin into the periphery, or that there is delayed action of rapamycin at sites in the brain.

Beneficial effects of quercetin on rat urinary bladder after spinal cord injury.

BACKGROUND: Spinal cord injury (SCI) leads to an inflammatory response and generates oxidative stress, which has deleterious effects on the function of several organ systems, including the urinary bladder. The present study was designed to investigate the putative beneficial effect of quercetin against SCI-induced bladder damage. MATERIALS AND METHODS: In order to induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10 was used. Injured animals were given either 20 mg/kg quercetin or vehicle 15 min post injury and repeated twice daily for 7 d. After decapitation, bladder strips were placed in organ bath and isometric contractions to carbachol (10(-8) to10(-4) M) were recorded. In order to examine oxidative tissue injury, luminol chemiluminescence, nitric oxide, malondialdehyde, and glutathione levels and superoxide dismutase, myeloperoxidase, and caspase 3 activities of bladder tissues were measured along with histologic evaluations. Proinflammatory cytokines tumor necrosis factor α, interleukin 1ß, and interleukin 6 were also assayed in blood samples. RESULTS: In the injured animals, the contractile responses of the bladder strips were lower than those of the control group and were reversed by treatment with quercetin. On the other hand, increase in nitric oxide, malondialdehyde, luminol chemiluminescence levels, and myeloperoxidase and caspase 3 activities of tissues in the SCI group were significantly reversed by quercetin treatment. Similarly, plasma cytokine levels, which were elevated in the vehicle-treated SCI group, were reduced with quercetin treatment. Furthermore, treatment with quercetin also prevented the depletion of tissue glutathione levels and superoxide dismutase activity seen in the SCI group. CONCLUSIONS: According to the results, quercetin exerts beneficial effects against SCI-induced oxidative damage through its anti-inflammatory and antioxidant effects.

The effects of Nigella sativa against oxidative injury in a rat model of subarachnoid hemorrhage.

OBJECTIVE: The aim of the study was to investigate the putative neuroprotective effect of Nigella sativa oil (NSO) treatment against subarachnoid hemorrhage (SAH) in rats. METHODS: To induce SAH, rats were injected with 0.3 ml blood into their cisterna magna. Male Wistar albino rats were divided as control, vehicle-treated SAH, and NSO-treated (0.2 ml/kg, intraperitoneally) SAH groups. Forty-eight hours after SAH induction, neurological examination scores were recorded and the rats were decapitated. Brain tissue samples were taken for blood brain barrier permeability, brain water content, or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na(+)-K(+)-ATPase activities. RESULTS AND DISCUSSION: On the second day of SAH induction, neurological examination scores were increased in SAH groups, while SAH caused significant decreases in brain GSH content and Na(+)-K(+)-ATPase activity, which were accompanied with significant increases in MDA levels and MPO activity. The histological observation showed vasospasm of the basillary artery. On the other hand, NSO treatment markedly improved the neurological scores while all oxidant responses were prevented, implicating that NSO treatment may be of therapeutic use in preventing oxidative stress due to SAH.

Alpha lipoic acid alleviates oxidative stress and preserves blood brain permeability in rats with subarachnoid hemorrhage.

The neuroprotective effect of alpha lipoic acid (ALA; 100 mg/kg, po), a dithiol antioxidant, on experimentally induced subarachnoid hemorrhage (SAH) was assessed in Wistar albino rats. Neurological examination scores recorded at the 48th h of SAH induction were increased in SAH groups, which were accompanied with significant increases in the formation of reactive oxygen species, DNA fragmentation ratios, malondialdehyde levels and myeloperoxidase activity, while significant decreases in the brain glutathione content and Na(+), K(+)-ATPase activity were observed. On the other hand, ALA treatment reversed all these biochemical indices as well as SAH-induced histopathological alterations. Increased brain edema, impaired blood-brain-barrier permeability and neurological scores were also improved by ALA treatment. The results demonstrate that ALA exerts neuroprotective effects via the enhancement of endogenous antioxidant enzyme activity, the inhibition of neutrophil accumulation and free radical generation, suggesting a therapeutic potential in reducing secondary injury after SAH in patients.

Neuroprotective effects of alpha-lipoic acid in experimental spinal cord injury in rats.

BACKGROUND: Oxidative stress is a mediator of secondary injury to the spinal cord following trauma. OBJECTIVE: To investigate the putative neuroprotective effect of alpha-lipoic acid (LA), a powerful antioxidant, in a rat model of spinal cord injury (SCI). METHODS: Wistar albino rats were divided as control, vehicle-treated SCI, and LA-treated SCI groups. To induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10 was used. Injured animals were given either 50 mg/kg LA or saline at 30 minutes postinjury by intraperitoneal injection. At 7 days postinjury, neurologic examination was performed, and rats were decapitated. Spinal cord samples were taken for histologic examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and DNA fragmentation. Formation of reactive oxygen species in spinal cord tissue samples was monitored by using a chemiluminescence (CL) technique. RESULTS: SCI caused a significant decrease in spinal cord GSH content, which was accompanied with significant increases in luminol CL and MDA levels, MPO activity, and DNA damage. Furthermore, LA treatment reversed all these biochemical parameters as well as SCI-induced histopathologic alterations. Conversely, impairment of the neurologic function caused by SCI remained unchanged. CONCLUSION: The present study suggests that LA reduces SCI-induced oxidative stress and exerts neuroprotection by inhibiting lipid peroxidation, glutathione depletion, and DNA fragmentation.

Cosmetovigilance: A New Concept for the Residency Curriculum.

Description Primary care physicians need to incorporate "cosmetovigilance" into their post-graduate curriculum to increase their residents' awareness of the adverse reactions induced by the use of cosmetic products, as well as promoting good reporting behavior.

Research and Data Mining During the COVID-19 Pandemic.

Description With the recent advances in information and technology systems, most developed countries have invested in building advanced systems for the management of electronic medical records. If the infrastructure of these systems are well designed, they both serve as an information resource for routine patient care and also serve as the primary backbone for medical research. This evidence became clear during the recent coronavirus pandemic, which has been a worldwide challenge since the beginning of 2020. Rapid spread of SARS-CoV-2 infections all over the world has resulted in tremendous health, economic and social ramifications, including social distancing, travel restrictions and closing of schools and businesses. Medical educational activities have shifted towards telemedicine, online learning and web-based meetings and conferences to prevent virus spread. While experimental lab research slowed, research with electronic medical records and databases accelerated in order to investigate the risk factors associated with COVID-19 and clinical management strategies to combat the disease. The urgency for COVID-related research has also lead to inconsistent and sometimes inaccurate output.

Importance of Awareness of Adverse Drug Reaction Reporting During the COVID-19 Pandemic.

Description Health care professionals hold the responsibility of reporting any adverse drug reactions in order to learn about new therapy and how best to safely care for our patients. The information derived from case publications and FDA MedWatch reports are essential to accumulate information and increase awareness for the possible risks of new drugs.

A New Journal to Publish Houses of Bricks: Introducing the HCA Healthcare Journal of Medicine.

Description Welcome to the HCA Healthcare Journal of Medicine, a new peer-reviewed scientific periodical dedicated to the care and improvement of human life by publishing and disseminating scholarly work focusing on innovation and enhanced quality, developing new knowledge in clinical care, and contributing to research in medical education.

Can Neuron Specific Enolase Be a Diagnostic Biomarker for Neuronal Injury in COVID-19?

Neuron specific enolase (NSE) is a biomarker for neuronal injury. However, increased levels in cerebrospinal fluid (CSF) and serum is associated with the clinical outcome in patients with head injury, ischemic stroke, intracerebral hemorrhage, cardiac arrest, anoxic encephalopathy, encephalitis, brain metastasis, and status epilepticus. Recently, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which started in China, rapidly evolved into the coronavirus disease 2019 (COVID-19) pandemic. Patients with COVID-19 have a wide range of symptoms varying from mild upper respiratory symptoms to severe illness requiring mechanical ventilation. While coronaviruses primarily target the human respiratory system, neurological symptoms are also observed in some patients. These include symptoms such as loss of taste and olfaction and diseases like cerebrovascular disorders including ischemic stroke and hemorrhages, encephalopathies, Guillain-Barré syndrome and acute disseminated encephalomyelitis. Here we report an observation from a patient whose NSE levels increased approximately four-fold in CSF. This finding was accompanied by increased white blood cell count and elevated protein in CSF indicating neuroinflammation. Thus, we suggest that NSE may be used as a CSF biomarker in COVID-19 patients with encephalopathy.

Early Aggressive Hydration Is Associated with Decreased Opioid Use and Readmission in Mild Acute Pancreatitis.

Background: Acute pancreatitis (AP) is one of the most common causes of hospital admissions due to gastrointestinal disorders. No pharmacologic agents have been proven to impact the prognosis, and the treatment still remains supportive with intravenous fluids for hydration. Although early hydration has been recommended for the management of mild AP, there is no consensus on the type, rate, and amount of the fluid replacement. Objective: In this study, we aimed to investigate the outcome of aggressive hydration in patients with AP. Methods: Retrospective data from patients admitted to 12 hospitals (2015-2017) was used for analysis. Five hundred patients who met the inclusion and exclusion criteria for mild AP were included. The subjects were classified into 3 groups based on the amount of intravenous fluids they received in the first 12 hours of admission: Hydration group A (0-1.5 ml/kg/h), Hydration group B (>1.5-3 ml/kg/h) and Hydration group C (>3 ml/kg/h). Laboratory test results on the second day of admission, length of stay (LOS) and opioid analgesic use on the last day were analyzed using a Chi-square test. A p-value of less than 0.05 was considered statistically significant. Results: Patients with aggressive hydration (>3 ml/kg/h) had a greater reduction in creatinine (mean difference = -0.05, p = 0.017) compared to those who received standard hydration (0-1.5 ml/kg/h). There was no significant difference in LOS among the three hydration groups. Patients with aggressive hydration were less likely to use opioid analgesics on the last day of hospitalization (23.9% vs. 35.3%, p = 0.044) compared to standard hydration. Patients with hydration were less likely to experience a readmission for any reason within 30 days (Odds ratio (OR) = 1.603, 95% CI, 1.064-2.414, p = 0.024) compared to those who received low hydration. Conclusions: Our findings showed that less narcotics were required for the patients receiving aggressive hydration in mild AP. On the other hand, early aggressive hydration is not widely implemented in community hospitals, despite beneficial effects.

The effects of riluzole on neurological, brain biochemical, and histological changes in early and late term of sepsis in rats.

OBJECTIVE: One of the underlying mechanisms of sepsis is thought to be the oxidative damage due to the generation of free radicals. Glutamate, the major excitatory amino acid in the brain, is known to play an important role in blood brain barrier (BBB) permeability, brain edema, and oxidative damage in pathological conditions. Riluzole, a glutamate release inhibitor, has been shown to have neuroprotective effects in several animal models. The aim of our study was to investigate the putative protective effect of riluzole against sepsis-induced brain injury. METHODS: Sepsis was induced by cecal ligation and puncture in Wistar albino rats. Sham operated (control) and sepsis groups received either saline or riluzole (6 mg/kg, s.c.) 30 min after the surgical procedure, and every 12 h as continuing treatment. The effect of riluzole on the survival rate, weight loss, fever, leukocyte count, brain edema, BBB permeability, oxidative damage, and histological observations were evaluated for early (6 h) and late (48 h) phase of sepsis. RESULTS: Riluzole, when administered 6 mg/kg s.c., diminishes the sepsis-induced augmentation in weight loss, body temperature, brain edema, increase in BBB permeability, oxidative damage, and brain injury that is observed histologically. Besides increasing the survival rate in sepsis, it has also improved neurological examination scores and the prognosis of the disease. CONCLUSION: According to the results of this study, riluzole appears to have a protective effect for sepsis-induced encephalopathy.

Melatonin reduces experimental subarachnoid hemorrhage-induced oxidative brain damage and neurological symptoms.

Oxidative stress has detrimental effects in several models of neurodegenerative diseases, including subarachnoid hemorrhage (SAH). This study investigated the putative neuroprotective effect of melatonin, a powerful antioxidant, in a rat model of SAH. Male Wistar albino rats were divided as control, vehicle-treated SAH, and melatonin-treated (10 mg/kg, i.p.) SAH groups. To induce SAH, 0.3 mL blood was injected into cisterna magna of rats. Forty-eight hours after SAH induction, neurological examination scores were measured and the rats were decapitated. Brain tissue samples were taken for blood-brain barrier (BBB) permeability, brain water content, histological examination, or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+-K+-ATPase activities. Formation of reactive oxygen species in brain tissue samples was monitored by using a chemiluminescence (CL) technique. The neurological examination scores were increased in SAH groups on the second day of SAH induction and SAH caused a significant decrease in brain GSH content and Na+-K+-ATPase activity, which was accompanied with significant increases in CL, MDA levels, and MPO activity. On the other hand, melatonin treatment reversed all these biochemical indices as well as SAH-induced histopathological alterations, while increased brain water content and impaired BBB were also reversed by melatonin treatment. This study suggests that melatonin, which can easily cross BBB, alleviates SAH-induced oxidative stress and exerts neuroprotection by preserving BBB permeability and by reducing brain edema.