Focal brain cooling suppresses spreading depolarization and reduces endothelial nitric oxide synthase expression in rats.

This study aimed to investigate the effects of focal brain cooling (FBC) on spreading depolarization (SD), which is associated with several neurological disorders. Although it has been studied from various aspects, no medication has been developed that can effectively control SD. As FBC can reduce neuronal damage and promote functional recovery in pathological conditions such as epilepsy, cerebral ischemia, and traumatic brain injury, it may also potentially suppress the onset and progression of SD. We created an experimental rat model of SD by administering 1 M potassium chloride (KCl) to the cortical surface. Changes in neuronal and vascular modalities were evaluated using multimodal recording, which simultaneously recorded brain temperature (BrT), wide range electrocorticogram, and two-dimensional cerebral blood flow. The rats were divided into two groups (cooling [CL] and non-cooling [NC]). Warm or cold saline was perfused on the surface of one hemisphere to maintain BrT at 37°C or 15°C in the NC and CL groups, respectively. Western blot analysis was performed to determine the effects of FBC on endothelial nitric oxide synthase (eNOS) expression. In the NC group, KCl administration triggered repetitive SDs (mean frequency = 11.57/h). In the CL group, FBC increased the duration of all KCl-induced events and gradually reduced their frequency. Additionally, eNOS expression decreased in the cooled brain regions compared to the non-cooled contralateral hemisphere. The results obtained by multimodal recording suggest that FBC suppresses SD and decreases eNOS expression. This study may contribute to developing new treatments for SD and related neurological disorders.

Cilostazol decreases duration of spreading depolarization and spreading ischemia after aneurysmal subarachnoid hemorrhage.

OBJECTIVE: Traditionally, angiographic vasospasm (aVS) has been thought to cause delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). However, successful treatment of aVS alone does not result in improved neurological outcome. Therefore, there may be other potential causes of poor neurological outcome, including spreading depolarization (SD). A recent study showed beneficial effects of cilostazol on DCI and neurological outcome. The present prospective clinical trial and experimental study focused on effects of cilostazol on SDs. METHODS: Fifty aSAH patients were treated with clip ligation and randomly assigned to a cilostazol (n = 23) or control group (n = 27). Effects of cilostazol on DCI, aVS, and SDs, measured with subdural electrodes, were examined. The effect of cilostazol on SD-induced perfusion deficits (spreading ischemia) was assessed in an aSAH-mimicking model. RESULTS: There was a trend for less DCI in the cilostazol group, but it did not reach our threshold for statistical significance (13.0% vs 40.0%, odds ratio = 0.266, 95% confidence interval [CI] = 0.059-1.192, p = 0.084). However, the total SD-induced depression duration per recording day (22.2 vs 30.2 minutes, ß = -251.905, 95% CI = -488.458 to -15.356, p = 0.043) and the occurrence of isoelectric SDs (0 vs 4 patients, ß = -0.916, 95% CI = -1.746 to -0.085, p = 0.037) were significantly lower in the cilostazol group. In rats, cilostazol significantly shortened SD-induced spreading ischemia compared to vehicle (Student t test, difference = 30.2, 95% CI = 5.3-55.1, p = 0.020). INTERPRETATION: Repair of the neurovascular response to SDs by cilostazol, as demonstrated in the aSAH-mimicking model, may be a promising therapy to control DCI. Ann Neurol 2018;84:873-885.

Decreased Flow Velocity with Transcranial Color-Coded Duplex Sonography Correlates with Delayed Cerebral Ischemia due to Peripheral Vasospasm of the Middle Cerebral Artery.

BACKGROUND AND OBJECTIVE: Despite intensive therapy, vasospasm remains a major cause of delayed cerebral ischemia (DCI) in worsening patient outcome after aneurysmal subarachnoid hemorrhage (aSAH). Transcranial Doppler (TCD) and transcranial color-coded duplex sonography (TCCS) are noninvasive modalities that can be used to assess vasospasm. However, high flow velocity does not always reflect DCI. The purpose of this study was to investigate the utility of TCD/TCCS in decreasing permanent neurological deficits. METHODS: We retrospectively enrolled patients with aSAH who were treated within 72 hours after onset. TCCS was performed every day from days 4 to 14. Peak systolic velocity (PSV), mean velocity (MV), and pulsatility index were recorded and compared between DCI and non-DCI patients. In patients with DCI, endovascular therapy was administered to improve vasospasm, which led to a documented change in velocity. RESULTS: Of the 73 patients, 7 (9.6%) exhibited DCI. In 5 of the 7 patients, DCI was caused by vasospasm of M2 or the more peripheral middle cerebral artery (MCA), and the PSV and MV of the DCI group were lower than those of the non-DCI group after day 7. Intra-arterial vasodilator therapy (IAVT) was performed for all patients with DCI immediately to increase the flow volume by the next day. CONCLUSIONS: Increasing flow velocity cannot always reveal vasospasm excluding M1. In patients with vasospasm of M2 or more distal arteries, decreasing flow velocity might be suggestive of DCI. IAVT led to increases in the flow velocity through expansion of the peripheral MCA.

Continuous Monitoring of Spreading Depolarization and Cerebrovascular Autoregulation after Aneurysmal Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is a prominent complication after aneurysmal subarachnoid hemorrhage (aSAH). Although vasospasm of proximal cerebral arteries has been regarded as the main cause of DCI, vasospasm of distal arteries, microthrombosis, impaired autoregulation, cortical spreading depolarization (CSD), and spreading ischemia are thought to be involved in DCI after aSAH. Here, we describe a patient with aSAH in whom CSD and cerebrovascular autoregulation were evaluated using simultaneous electrocorticography and monitoring of the pressure reactivity index (PRx) after surgical clipping of a ruptured posterior communicating artery aneurysm. In this patient, a prolonged duration of CSD and elevation of PRx preceded delayed neurological deficit. Based on this observation, we propose a relationship between these factors and DCI. Assessment of cerebrovascular autoregulation may permit detection of the inverse hemodynamic response to cortical depolarization. Detection of DCI may be achieved through simultaneous monitoring of CSD and PRx in patients with aSAH.

Importance of Early Postoperative Body Temperature Management for Treatment of Subarachnoid Hemorrhage.

BACKGROUND: The importance of acute-phase brain temperature management is widely accepted for prevention of exacerbation of brain damage by a high body temperature. METHODS: In this study, we investigated the influence of body temperature in the early postoperative period on the outcomes of 62 patients with subarachnoid hemorrhage who were admitted to our department. Body temperature was measured from day 4 to day 14 after onset. The patients were divided into those treated with surgical clipping (clip group) and coil embolization (coil group), those graded I-III (mild) and IV-V (severe) based on the Hunt & Hess classification on admission, those with and without development of delayed cerebral ischemia (DCI), and those with favorable and poor outcomes. Body temperatures throughout the hospital stay were compared in each group. RESULTS: There was no significant difference in body temperature between the clip and coil groups or between the mild and severe groups, but body temperature was significantly higher in patients with DCI compared to those without DCI, and in patients with a poor outcome compared to those with a favorable outcome. CONCLUSIONS: Fever in the early postoperative period of subarachnoid hemorrhage is associated with development of DCI and a poor outcome.

Strategies and Pitfalls of Motor-Evoked Potential Monitoring during Supratentorial Aneurysm Surgery.

BACKGROUND: The aims of this study were to reveal the strategies and pitfalls of motor-evoked potential (MEP) monitoring methods during supratentorial aneurysm surgery, and to discuss the drawbacks and advantages of each method by reviewing our experiences. METHODS: Intraoperative MEP monitoring was performed in 250 patients. Results from 4 monitoring techniques using combinations of 2 stimulation sites and 2 recording sites were analyzed retrospectively. RESULTS: MEP was recorded successfully in 243 patients (97.2%). Direct cortical stimulation (DCS)-spinal recorded MEP (sMEP) was used in 134 patients, DCS-muscle recorded MEP (mMEP) in 97, transcranial electrical stimulation (TES)-mMEP in 11 and TES-sMEP in 1. TES-mMEP during closure of the skull was used in 21 patients. DCS-mMEP was able to detect waveforms from upper and/or lower limb muscles. Alternatively, DCS-sMEP (direct [D]-wave) could accurately estimate amplitude changes. A novel "early warning sign" indicating ischemia was found in 21 patients, which started with a transiently increased amplitude of D-wave and then decreased after proximal interruption of major arteries. False-negative findings in MEP monitoring in 2 patients were caused by a blood insufficiency in the lenticulostriate artery and by a TES-sMEP recording, respectively. CONCLUSIONS: The results of this study suggest that to perform accurate MEP monitoring, DCS-mMEP or DCS-sMEP recording should be used as the situation demands, with combined use of TES-mMEP recording during closure of the skull. DCS-sMEP is recommended for accurate analysis of waveforms. We also propose a novel "early warning sign" of blood insufficiency in the D-wave.

Cranioplasty and Duraplasty with Transcranial Color-Coded Duplex Sonography after Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Transcranial color-coded duplex sonography (TCCS) is a noninvasive technique for monitoring of cerebral vasospasm after neurosurgery for aneurismal subarachnoid hemorrhage. In this surgery, surgical materials are used. The goal of the study was to identify materials that can be used with ultrasound and to propose methods for cranioplasty and duraplasty using materials that permit TCCS. METHODS: The chosen neurosurgical materials were titanium mesh plate (TMP), Gore-tex, SEAMDURA, gelatinous sponge, and oxidized cellulose. B-mode imaging was recorded with the materials placed between urethane resin 10 mm in diameter and the urethane phantom model. TCCS was performed to detect middle cerebral artery flow through TMP and Gore-tex. RESULTS: TMP and SEAMDURA permitted penetration of ultrasound in B-mode and Doppler imaging, but the other materials did not do so. CONCLUSIONS: A postcraniotomy window (PCW) on a line extending from the horizontal portion of M1 using only TMP permitted flow imaging with TCCS. In external decompression, TCCS was effective only without use of Gore-tex around the postcraniotomy window. This method allows the middle cerebral artery flow to be detected easily.

Relationship between Aging and Enlargement of Intracranial Aneurysms.

BACKGROUND: To predict possible enlargement of cerebral aneurysms with aging, we retrospectively analyzed aneurysm size in relation to patient age and aneurysm site. METHODS: We included 1332 unruptured and 2362 ruptured aneurysms detected in patients from the Yamaguchi Prefecture, Japan, from 1995 to 2005. RESULTS: Age-specific site distribution was not found in the unruptured aneurysms. In the ruptured aneurysms, the incidence of anterior communicating artery (AComA) aneurysms was higher than that of internal carotid posterior communicating (ICPC) artery aneurysms among the patients aged 40-49 years (32.6% versus 14.4%), whereas the difference was small among the elderly patients aged 70-79 years (25.8% versus 24.9%). In the AComA aneurysms, either in the unruptured or ruptured cases, no age-related change in size was found. In the ICPC aneurysms, either in the unruptured or in the ruptured cases, the size of the aneurysms 7 mm or larger increased with age. CONCLUSIONS: The sizes of AComA aneurysms may remain stable with aging. Therefore, the risk of rupture may be similar in young and elderly patients. Meanwhile, ICPC artery aneurysms may continue to grow throughout the patient's life, with an increasing risk of rupture.

A novel trigger for cholesterol-dependent smooth muscle contraction mediated by the sphingosylphosphorylcholine-Rho-kinase pathway in the rat basilar artery: a mechanistic role for lipid rafts.

Hyperlipidemia is a risk factor for abnormal cerebrovascular events. Rafts are cholesterol-enriched membrane microdomains that influence signal transduction. We previously showed that Rho-kinase-mediated Ca(2+) sensitization of vascular smooth muscle (VSM) induced by sphingosylphosphorylcholine (SPC) has a pivotal role in cerebral vasospasm. The goals of the study were to show SPC-Rho-kinase-mediated VSM contraction in vivo and to link this effect to cholesterol and rafts. The SPC-induced VSM contraction measured using a cranial window model was reversed by Y-27632, a Rho-kinase inhibitor, in rats fed a control diet. The extent of SPC-induced contraction correlated with serum total cholesterol. Total cholesterol levels in the internal carotid artery (ICA) were significantly higher in rats fed a cholesterol diet compared with a control diet or a ß-cyclodextrin diet, which depletes VSM cholesterol. Western blotting and real-time PCR revealed increases in flotillin-1, a raft marker, and flotillin-1 mRNA in the ICA in rats fed a cholesterol diet, but not in rats fed the ß-cyclodextrin diet. Depletion of cholesterol decreased rafts in VSM cells, and prevention of an increase in cholesterol by ß-cyclodextrin inhibited SPC-induced contraction in a cranial window model. These results indicate that cholesterol potentiates SPC-Rho-kinase-mediated contractions of importance in cerebral vasospasm and are compatible with a role for rafts in this process.

Adverse events after unruptured cerebral aneurysm treatment: a single-center experience with clipping/coil embolization combined units.

BACKGROUND: Indications of clipping (Clip) or coil embolization (Coil) for unruptured cerebral aneurysms (uAN) was not elaborated because prediction of rupture and risk of treatment are difficult. This study aims to determine the risk-benefit analysis of treating uAN by a comprehensive and retrospective investigation of the adverse events and sequelae in patients treated by our Clip/Coil combined units. METHODS: Clip and Coil were performed in 141 and 80 patients, respectively; Clip for middle cerebral artery AN and Coil for paraclinoid or basilar apex AN. Worsening of modified Rankin scale or mini-mental state examination was defined as major morbidity. Minor morbidity or transient morbidity was defined as other neurologic deficits. Mortality and these morbidities were considered as serious adverse events. Convulsion or events outside the brain were defined as mild adverse events. RESULTS: Total mortality and major morbidity were low. Incidence of serious adverse events was not significantly different between the Clip and Coil (17 patients [12.1%] and 6 patients [7.5%]), but the number of total adverse events was significantly different (32 patients [22.7%] in Clip vs. 8 patients [10.0%] in Coil). Because mild morbidities were significantly more frequent in the Clip (20 patients [14.2%]) compared with the Coil (2 patients [2.5%]). Convulsion occurred in 11 (7.8%) patients in the Clip but none in the Coil. CONCLUSIONS: Our combined unit decreased the occurrence of mortality/major morbidity; however, minor adverse effects were common, especially in the Clip group because of many intrinsic problems of Clip itself. This result suggests further consideration for the treatment modality for uAN.

Cognitive dysfunction might be improved in association with recovered neuronal viability after intracranial meningioma resection.

Intracranial meningiomas are the most common types of neoplasms that cause mental disorders. Although higher brain function can be restored and even improved in some patients after tumor resection, the mechanisms remain unclear. We investigated changes in the brains of patients after resection of an intracranial meningioma using (123)I-Iomazenil (IMZ)-single photon emission computed tomography (SPECT). Ten patients underwent IMZ-SPECT within 4 weeks before and 3 months after intracranial meningioma resection. Changes in IMZ accumulation in brain parenchyma were assessed as ratios of counts in the lesion-to-contralateral hemisphere (L/C ratios). Mean Mini-Mental State Examination scores before and after resection of 19.9±11.4 vs. 26.5±3.8, respectively (p=0.03) indicated that the cognitive function of these patients was significantly improved after tumor resection. The average L/C ratios calculated from image counts of IMZ were 0.92±0.05 and 0.98±0.02 before and after surgery, respectively. The L/C ratio of IMZ accumulation was significantly decreased after tumor resection (p=0.0003). In contrast, regional cerebral blood flow calculated from (123)I-Iodoamphetamine-SPECT images did not significantly differ after tumor resection. The recovered binding potential of IMZ in brain parenchyma surrounding the tumor bulk after resection indicates that the viability of central benzodiazepine receptors was reversibly depressed and recoverable after release from compression by the tumor. The recovered neuronal viability revealed by IMZ-SPECT might be responsible for the improved cognitive function after intracranial meningioma resection.

A prospective, multicenter, randomized study of the efficacy of eicosapentaenoic acid for cerebral vasospasm: the EVAS study.

OBJECTIVE: The sphingosylphosphorylcholine-Rho-kinase pathway plays an important role in Ca(2+) sensitization of vascular smooth muscle contraction. Eicosapentaenoic acid (EPA) inhibits sphingosylphosphorylcholine -Rho-kinase-activated Ca(2+)-sensitization in vitro and in subarachnoid hemorrhage (SAH) models in vivo and has also been shown to inhibit the occurrence of cerebral vasospasm (CIV) after the onset of SAH in a prospective, nonrandomized study. The current prospective, multicenter, randomized study was performed to confirm the preventive effects of EPA on CIV in patients with SAH. METHODS: The trial population comprised 162 patients who underwent surgical clipping within 72 hours of the onset of SAH. Of these patients, 81 received 2700 mg/day EPA from the day after surgery until day 30 (EPA group), and 81 did not receive EPA (control group). The primary end point was the occurrence of symptomatic vasospasm (SV) or cerebral infarction caused by CIV. RESULTS: The occurrences of SV (15% vs. 30%; P = 0.022) and CIV (7% vs. 21%; P = 0.012) were lower in the EPA group. Multivariate analysis revealed an adjusted odds ratio of 0.39 (95% confidence interval, 0.17-0.89; P = 0.028) for SV inhibition by EPA and 0.27 (95% confidence interval, 0.09-0.72; P = 0.012) for CIV inhibition. CONCLUSIONS: These results indicate that oral EPA reduces the frequency of SV and CIV after the onset of aneurysmal SAH.

Fragmental or massive embolization in cardiogenic stroke caused by nonvalvular atrial fibrillation.

BACKGROUND: After cardioembolic stroke (CES), left atrial thrombus (LAT) is detected by transesophageal echocardiography (TEE) in some cases but not in others. We propose that there are 2 types of embolization in CES: fragmental and massive embolization. METHODS: Consecutive patients with nonvalvular atrial fibrillation (AF) of acute CES or transient ischemic attack (TIA) were prospectively enrolled in the study between May 2009 and July 2011. TEE was performed within 7 days of admission. The patients were classified into 2 groups: those with occlusion of the main trunk (internal carotid artery, M1, and basilar artery; group M) and those with occlusion of other distal arteries (group D). Clinical features were compared between patients who did and did not have a thrombus on TEE. RESULTS: Of the 41 patients in the study, 21 were in group M and 20 were in group D. Age, sex, and treatment with tissue plasminogen activator did not differ significantly between the 2 groups. The rate of detection of LAT was significantly higher in group D (14% v 65%; P < .001). CONCLUSIONS: Patients with distal artery occlusion had a significantly higher rate of LAT compared to those with main trunk occlusion. Distal artery occlusion in CES therefore tends to result from fragmental embolization and is associated with a remnant LAT, with which there may be a concern of a risk of early recurrence.

Postoperative dural arteriovenous fistula in a patient with Cowden disease: a case report.

We report the case of a 37-year-old male with Cowden disease that caused a gradual neurological deficit because of rupture of a brain stem cavernous hemangioma. Removal of the hemangioma and hematoma was performed with an infrafacial triangle approach. Nine months after the operation, magnetic resonance imaging showed abnormal vessels on the cerebellar surface. Digital subtraction angiography showed a dural arteriovenous fistula (dAVF) from part of the meningeal artery to the ectatic inferior vermian vein with cortical reflux. After embolization, surgical obliteration of the dAVF was performed. Surgical findings showed neovascularization in the thickened dura, in which dural vessels shunted to cerebellar vessels through adhesion between the dura mater and cerebellar surface. Therefore, the thickened dura was removed with the cerebellar surface. This case suggests that postoperative angiogenesis may cause arteriovenous fistula in patients with Cowden disease.

Repeated cerebral ischemia caused by extracranial carotid artery dolichoectasia.

We report the case of a 67-year-old man with repeating cerebral embolism caused by a dolichoectatic right common carotid artery. The patient had a history of hypertension, hypercholesterolemia, cigarette smoking, and a postoperative abdominal aortic aneurysm. He presented with a sudden onset of weakness of the left arm and leg. Magnetic resonance imaging revealed old and fresh infarction in the right cerebral hemisphere. Carotid duplex ultrasonography showed a dolichoectatic right common carotid artery with a maximum diameter of 39 mm with thick plaque and strong spontaneous echo contrast. The flow velocity was considerably reduced, which caused thrombus formation, and strong antithrombotic therapy was required. This case provides a rare example of ischemic stroke caused by extracranial carotid artery dolichoectasia.

Multicenter prospective cohort study on volume management after subarachnoid hemorrhage: hemodynamic changes according to severity of subarachnoid hemorrhage and cerebral vasospasm.

BACKGROUND AND PURPOSE: Systemic circulation management has not been established for patients with poor grade aneurysmal subarachnoid hemorrhage (SAH) or delayed cerebral ischemia (DCI) after SAH. The aims of the study were to examine hemodynamic variables in these patients and to establish treatment strategies. METHODS: A multicenter prospective cohort study of hemodynamic variables from days 1 to 14 was performed using a transpulmonary thermodilution system (PiCCO Plus). Parameters were analyzed by Mann-Whitney test. Multivariate analysis was performed to identify parameters involved in onset of DCI. RESULTS: The subjects were 204 patients, including 138 with poor grade SAH (World Federation of Neurological Surgeons grades IV and V) and 52 who developed DCI. The extravascular lung water index, pulmonary vascular permeability index, and systemic vascular resistance index were significantly greater in patients with poor grade SAH compared with those with good grade SAH (World Federation of Neurological Surgeons I-III) on day 2 (P=0.049, P=0.039, and P=0.038). Cardiac index was significantly lower in patients with poor grade SAH on days 1 and 2 (P=0.027 and P=0.011). In patients with DCI, the global end-diastolic volume index was significantly lower than in those without DCI on days 3 to 5 (P=0.0053; P=0.048; and P=0.048). In multivariate analysis, median global end-diastolic volume index, cardiac index, and systemic vascular resistance index at an early stage of SAH (days 3-6) were independently related to onset of DCI (P=0.023, P=0.013, and P=0.003). CONCLUSIONS: Patients with poor grade SAH developed heart failure-like afterload mismatch at an early stage, and those with DCI had decreased global end-diastolic volume index (hypovolemia) in the early stage of SAH. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: UMIN000003794.

Cooling treatment transiently increases the permeability of brain capillary endothelial cells through translocation of claudin-5.

The blood-brain-barrier (BBB) is formed by different cell types, of which brain microvascular endothelial cells are major structural constituents. The goal of this study was to examine the effects of cooling on the permeability of the BBB with reference to tight junction formation of brain microendothelial cells. The sensorimotor cortex above the dura mater in adult male Wistar rats was focally cooled to a temperature of 5 °C for 1 h, then immunostaining for immunoglobulin G (IgG) was performed to evaluate the permeability of the BBB. Permeability produced by cooling was also evaluated in cultured murine brain endothelial cells (bEnd3) based on measurement of trans-epithelial electric resistance (TEER). Immunocytochemistry and Western blotting of proteins associated with tight junctions in bEnd3 were performed to determine protein distribution before and after cooling. After focal cooling of the rat brain cortex, diffuse immunostaining for IgG was observed primarily around the small vasculature and in the extracellular spaces of parenchyma of the cortex. In cultured bEnd3, TEER significantly decreased during cooling (15 °C) and recovered to normal levels after rewarming to 37 °C. Immunocytochemistry and Western blotting showed that claudin-5, a critical regulatory protein for tight junctions, was translocated from the membrane to the cytoplasm after cooling in cultured bEnd3 cells. These results suggest that focal brain cooling may open the BBB transiently through an effect on tight junctions of brain microendothelial cells, and that therapeutically this approach may allow control of BBB function and drug delivery through the BBB.

Seasonal variation in the incidence of aneurysmal subarachnoid hemorrhage associated with age and gender: 20-year results from the Yamaguchi cerebral aneurysm registry.

BACKGROUND: This study was a cerebral aneurysm registry study conducted in a region with few climatic differences. Based on data collected for over 20 years, seasonal variations and characteristics of subarachnoid hemorrhage (SAH) due to ruptured aneurysms were analyzed. METHODS: This study included 5,007 patients in the Yamaguchi Prefecture with aneurysmal SAH between 1986 and 2005. Incidence rates by month, sex, age, severity, and aneurysm site were analyzed. RESULTS: In women, seasonal variation was observed, in particular among those aged ≥50 years. Among those aged 50-69 years, the highest incidence was in October, and the nadir was in June (peak-to-trough ratio = 1.72). At age ≥70 years, this was slightly different, with the highest incidence in December and the nadir in July (peak-to-trough ratio = 1.48). However, there was no seasonal variation in men overall; it was limited to elderly men at age ≥70 years, with the highest incidence in January and the nadir in July (peak-to-trough ratio = 2.9). Aneurysm site and severity showed no relationship with seasonal variation. CONCLUSION: The present study shows seasonal variations in the onset of SAH. Seasonal variations in SAH differed depending on age and sex.

Neuroprotective effects of focal brain cooling on photochemically-induced cerebral infarction in rats: analysis from a neurophysiological perspective.

Although systemic hypothermia provides favorable outcomes in stroke patients, it has only been adopted in a limited number of patients because of fatal complications. To resolve these issues, focal brain cooling (FBC) has recently drawn attention as a less-invasive treatment for brain injuries. Therefore, we investigated whether FBC has a favorable effect on focal cerebral ischemia (FCI). Male-adult-Wistar rats were used. Under general anesthesia, a small burr hole was made and FCI was induced in the primary sensorimotor area (SI-MI) using photothrombosis. An additional craniotomy was made over the SI-MI and FBC was performed at a temperature of 15°C for 5h. Electrocorticograms (ECoG) were recorded on the border cortex of the ischemic focus. Thereafter, rats were sacrificed and the infarct area was measured. In another experiment, rats were allowed to recover for 5 days after cooling and neurobehavioral function was evaluated. FBC suppressed all ECoG frequency bands during and after cooling (p<0.05), except for the delta frequency band in the precooling versus rewarming periods. The injured areas in the cooling and non-cooling groups were 0.99±0.30 and 1.71±0.54 mm(2), respectively (p<0.03). The grip strength at 2 days after surgery was preserved in the cooling group (p<0.05). We report the novel finding that epileptiform discharges were suppressed in the ischemic border, the infarct area was reduced and neurobehaviour was preserved by FBC. These results indicate that FBC is neuroprotective in the ischemic brain and has demonstrated therapeutic potential for cerebral infarction.