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Statins influence immune system activities through mechanisms independent of their lipid-lowering properties. T cells can be subdivided based on cytokine secretion patterns into two subsets: T-helper cells type 1 (Th1) and type 2 (Th2). Independent laboratory studies have shown statins to be potent inducers of a Th2 switch in immune cell response and be neuroprotective in several models of central nervous system (CNS) disease. This study was the first to evaluate the immune modulating effects of statins in subarachnoid hemorrhage (SAH).Simvastatin was administered to rats intraperitoneally in two dosages (1 and 20 mg/kg) 30 min after the induction of SAH using endovascular perforation. Neurological scores were assessed 24 h later. Animals were then sacrificed, and samples of cortex and brain stem were tested for expression of the T-regulatory cell cytokine transforming growth factor (TGF) β1, as well as interleukin (IL) 1β, a proinflammatory cytokine associated with Th1 immune responses. The presence of TGF-β1 secreting T cells was evaluated with the use of brain slices.SAH significantly impaired neurological function in all SAH groups (treated and untreated) versus sham. Animals treated with high-dose simvastatin had less neurological impairment than both untreated and low-dose groups. Cortical and brain-stem levels of TGF-β1 were significantly elevated following SAH in the high-dose group. IL-1β was significantly elevated following the induction of SAH but was inhibited by high-dose simvastatin. Double-labeled fluorescent immunohistochemical data demonstrated the presence of lymphocytes in the subarachnoid and perivascular spaces following SAH. Expression of TGF-β1 by lymphocytes was markedly increased following treatment with high-dose simvastatin.The present study elucidated the potential role of a Th2 immune switch in statin provided neuroprotection following SAH.

Background: Subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) contributes to delayed ischemic neurological deficits, one of whose key pathologic manifestation is the blood–brain barrier (BBB) disruption. Although post-SAH BBB breakdown is a self-repairable phenomenon, the molecular pathways are unknown. We determined the role of osteopontin (OPN), a pleiotropic extracellular matrix glycoprotein, in the post-SAH BBB disruption in rats.

Objects: We determined effects of recombinant OPN (r-OPN), a pleiotropic extracellular matrix protein, on blood-brain barrier (BBB) disruption and matrix metalloproteinase (MMP)-9 activation after subarachnoid hemorrhage (SAH) in rats.

Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors, commonly known as statins, are widely used clinically for their lipid lowering properties. Recent experimental evidence shows that statins are also effective in ameliorating cerebral vasospasm, which occurs as sequelae of subarachnoid hemorrhage. This literature re- view focuses on the literature-based putative mechanisms involvedinstatinmediatedattenuationofcerebral vasospasm, such as eNOS, vascular inflammation, apoptosis, especially the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway from our experimental study.

Acute subdural hematoma (ASDH) patients presenting in a severe condition tend to have poor outcomes due to the significant brain edema required to maintain the ICP at less than 20–25 mmHg. This study compared the surgical outcomes of 16 critically ill patients with ASDH who underwent hematoma irrigation with trephination therapy (HITT) based on their initial ICP values. The initial mean GCS score upon admission was four. A unilateral dilated pupil was seen in one and bilateral dilated pupils were seen in seven patients. The co-existence of a brain contusion was seen in seven patients, brain swelling was noted in six patients, and both basal cistern effacement and a midline shift greater than 5 mm were observed in all patients. The mean initial ICP value was 45mmHg (range: 3 to 85 mmHg). Ten patients (62.5%) underwent a rapid external decompression to evacuate the hematoma. By using the Glasgow Outcome Scale upon discharge a score of good recovery (GR) was assigned to two (12.5 %), moderate disability (MD) to four (25.0 %), vegetative state (VS) to two (12.5 %), and death (D) to eight (50.0 %) patients. All six patients who showed an initial ICP greater than 60 mmHg died despite intensive care. Eight patients who showed an initial ICP less than 40 mmHg had a favorable outcome, but two patients deteriorated due to a traumatic cerebrovascular disorder. It seems that the initial ICP monitoring with HITT for ASDH patients in critical condition may be an important factor for predicting both surgical outcome and clinical course.

Acute epidural hematomas (AEDH) are generally managed with rapid surgical hematoma evacuation and bleeding control. However, the surgical outcome of patients with serious brain edema is poor. This study reviewed the clinical outcome for AEDH patients and evaluated the efficacy of the DC, especially in patients with associated massive brain swelling. Eighty consecutive patients surgically treated with AEDH were retrospectively assessed. The patients were divided into two groups: (a) hematoma evacuation (HE: 46 cases) and (b) HE+ an external decompression (ED: 34 cases). The medical charts, operative findings, radiological findings, and operative notes were reviewed. In the poor outcome group, there were 18 patients (72%), with a GCS score of less than 8 (severe injury), and 22 patients (88%) who showed pupil abnormalities. Many more patients showed a midline shift, basal cistern effacement, and brain contusion in comparison to the favorable outcome group. In the favorable outcome group, almost all of the patients (98%) showed less than 12 mm of a midline shift. The influential factors may be age, GCS, pupil abnormalities, size, midline shift, basal cistern effacement, coincidence of contusion and swelling. We conclude that an A DC may be effective to manage the AEDH patients with cerebral contusion or massive brain swelling.

Background Cerebral vasospasm is a common sequelae of subarachonoid hemorrhage (SAH), however, the mechanism of cerebral vasospasm is still unclear. Recently, statins have been shown to have efficacy in ameliorating cerebral vasospasm. The present study investigates whether simvastatin attenuates cerebral vasospasm after subarachnoid hemorrhage (SAH) via upregulation of the PI3K/Akt pathway Methods 47 adult male Sprague-Dawley rats were divided into 6 groups: sham-operated, SAH treated with vehicle, SAH treated with low dose simvastatin (1 mg/kg), high dose simvastatin (20 mg/kg), SAH treated with simvastatin plus the PI3K inhibitor (wortmannin), and sham-operated plus wortmannin. Simvastatin was administered intraperitoneally 30 minutes after SAH created by the standard endovascular perforation model. Histological parameters of the ipsilateral internal carotid artery (ICA - diameter, perimeter, and wall thickness) and neurological score were

Background Aneurysmal subarachnoid hemorrhage (SAH) is a devastating disease that is associated with significant morbidity and mortality. There is substantial evidence to suggest that oxidative stress is significant in the development of acute brain injury following SAH. Melatonin is a strong antioxidant that has low toxicity and easily passes through the BBB. Previous studies have shown that melatonin provides neuroprotection in other models of CNS injury. Methods This experiment evaluates melatonin as a neuroprotectant against early brain injury following SAH. The endovascular perforation model of SAH was performed in male Sprague Dawley rats followed by the administration of melatonin two hours after the insult. Mortality and brain water content were assessed 24 after SAH. Findings A significant reduction in 24 h mortality was seen following treatment with 150 mg/kg of melatonin. Brain water content was evaluated in the high dose treatment group to see if a reduction in brain edema was associated with reduced mortality. High dose melatonin tended to reduce brain water content following SAH. Conclusions Large doses of melatonin significantly reduced mortality and brain water content in rats following SAH.

Endovascular coiling has become a standard option in addition to surgical clipping in the treatment modality for cerebral aneurysms; thus, it is important to assess the effect of these different treatment options on vasospasm after aneurismal subarachnoid haemorrhage (SAH). Although several recent studies have suggested that the incidence of vasospasm is lower in patients undergoing aneurysmal coiling as opposed to clipping, other studies have had conflicting results. Through multivariate analysis, we have reviewed 522 patients with ruptured intracranial aneurysms, treated consecutively in our centre, to determine whether the incidence of vasospasm and clinical outcomes have differed between patients treated with clipping and coil occlusion. As a result, there was no significant difference in the occurrence of symptomatic vasospasm and overall outcome between the two treatments. The patients with better Hunt & Kosnik (H&K) grades (OR 1.19, 95% CI 1.01–1.64), rupture of posterior circulation aneurysms (OR 0.23, 95% CI 0.07–0.75), and elderly age (OR 0.97, 95% CI 0.95–0.98) were less likely to suffer from angiographic vasospasm.