Inhibition of P2X4 and P2X7 receptors improves histological and behavioral outcomes after experimental traumatic brain injury in rats.

Release of large amounts of adenosine triphosphate (ATP), a gliotransmitter, into the extracellular space by traumatic brain injury (TBI) is considered to activate the microglia followed by release of inflammatory cytokines resulting in excessive inflammatory response that induces secondary brain injury. The present study investigated whether antagonists of ATP receptors (P2X4 and/or P2X7) on microglia are beneficial for reducing the post-injury inflammatory response that leads to secondary injury, a prognostic aggravation factor of TBI. Adult male Sprague-Dawley rats were subjected to cortical contusion injury (CCI) and randomly assigned to injury and drug treatment conditions, as follows: i) No surgical intervention (naïve group); ii) dimethyl sulfoxide treatment after CCI (CCI-control group); iii) 5-BDBD (antagonist of P2X4 receptor) treatment after CCI (CCI-5-BDBD group); iv) CCI-AZ11645373 (antagonist of P2X7 receptor) treatment after CCI (CCI-AZ11645373 group); v) or 5-BDBD and AZ11645373 treatment after CCI (CCI-5-BDBD + AZ11645373 group). In the CCI-5-BDBD, CCI-AZ11645373, and CCI-5-BDBD + AZ11645373 groups, expression of activated microglia was suppressed in the ipsilateral cortex and hippocampus 3 days after the CCI. Western blotting with ionized calcium-binding adaptor molecule 1 antibody revealed that administration of CCI-5-BDBD and/or CCI-AZ11645373 suppressed expression of microglia and reduced expression of inflammatory cytokine mRNA 3 days after the CCI. Furthermore, the plus maze test, which reflects the spatial memory function and involves the hippocampal function, showed improvement 28 days after secondary injury to the hippocampus. These findings confirmed that blocking the P2X4 and P2X7 receptors, which are ATP receptors central in gliotransmission, suppresses microglial activation and subsequent cytokine expression after brain injury, and demonstrates the potential as an effective treatment for reducing secondary brain injury.

Glibenclamide reduces secondary brain injury in a SAH rat model by reducing brain swelling and modulating inflammatory response.

BACKGROUND: Early brain injury (EBI) after subarachnoid hemorrhage (SAH) is a new therapeutic target. Sulfonylurea receptor 1 (SUR1) is expressed in nerve cells, glial cells, and vascular endothelial cells in EBI. SUR1 promotes intracellular inflow of Na and Ca ions, resulting in cell swelling and depolarization, and finally cell death. Glibenclamide reduced cerebral edema and mortality in a basic study of cerebral ischemia. However, the effects of glibenclamide on EBI have not been fully elucidated. This study examined the inhibitory effect of glibenclamide on EBI. METHODS: Rats were divided into the sham group, SAH-control group, and SAH-glibenclamide group. The water content of the brain was measured using the dry-wet method. In addition, the brain was divided into the cortex, putamen, and hippocampus, and expression of inflammatory cytokines was evaluated by the polymerase chain reaction method. In addition, microglia in the brain were evaluated immunohistologically. RESULTS: Water content of the brain was significantly decreased in the SAH-glibenclamide group compared to the SAH-control group. Interleukin-1beta (IL-1ß), tumor necrosis factor alpha (TNFα), and nuclear factor-kappa B significantly increased in the cerebral cortex after SAH. IL-1ß and TNFα in the cortex were significantly decreased in the SAH-glibenclamide group compared to the SAH-control group. Immunohistochemical staining confirmed that SAH causes extensive microglial activation in the brain, which was suppressed by glibenclamide. CONCLUSIONS: The present study showed that glibenclamide suppressed cerebral edema and activation of microglia and hypersecretion of inflammatory cytokines. Glibenclamide is a potential therapeutic method which may significantly improve the functional prognosis.

Anti-inflammatory effect of P2Y1 receptor blocker MRS2179 in a rat model of traumatic brain injury.

The aim of the current study was to determine the effects of cerebral contusion injury with purinergic adenosine triphosphate Y1 (P2Y1) receptor blockers on postinjury inflammatory responses. Adenosine triphosphate (ATP) is released into the extracellular space in several in vivo models, including traumatic brain injury. Released ATP triggers neuroinflammation via activation of microglial cells. P2Y1 receptor blockers were reported to suppress extracellular ATP elevation in several disease models through inhibition of cellular ATP release. In addition to the beneficial effects of inflammation, excess inflammatory reactions cause secondary damage and aggravate outcomes. Here, we assessed the effect of the selective P2Y1 receptor blocker MRS2179 on its potential to prevent posttraumatic inflammation in a rat cerebral contusion model. Cerebral contusion injury was induced in the rat cerebral cortex. Either MRS2179 or artificial cerebral spinal fluid as a control was administered in situ into the center of contused tissue via a subcutaneously implanted osmotic pump. Galectin 3, a marker of microglia and proinflammatory cytokines, was measured 1, 3 and 7 days following injury. Another group of rats was assessed for behavioral performance up to 28 days after injury, including the beam walk test, neurological response test and plus maze test. The Galectin 3 levels in the cortex around the contusion cavity and in the cortex far from the contusion cavity were significantly suppressed by MRS2179 administration on postinjury Days 1 and 3 (p < 0.05). However, administration of MRS2179 failed to improve behavioral outcome. Administration of MRS2179 successfully suppressed microglial activation in a traumatic brain injury model, which will be a potent treatment option in the future. Further study is required to conclude its therapeutic effects.

Massive efflux of adenosine triphosphate into the extracellular space immediately after experimental traumatic brain injury.

The aim of the current study was to determine effects of mild traumatic brain injury (TBI), with or without blockade of purinergic ATP Y1 (P2Y1) receptors or store-operated calcium channels, on extracellular levels of ATP, glutamate, glucose and lactate. Concentrations of ATP, glutamate, glucose and lactate were measured in cerebral microdialysis samples obtained from the ipsilateral cortex and underlying hippocampus of rats with mild unilateral controlled cortical impact (CCI) or sham injury. Immediately after CCI, a large release of ATP was observed in the cortex (3.53-fold increase of pre-injury value) and hippocampus (2.97-fold increase of pre-injury value), with ATP returning to the baseline levels within 20 min post-injury and remaining stable for during the 3-h sampling period. In agreement with the results of previous studies, there was a significant increase in glutamate 20 min after CCI, which was concomitant with a decrease in extracellular glucose (20 min) and an increase in lactate (40-60 min) in both brain regions after CCI. Addition of a selective P2Y1 receptor blocker (MRS2179 ammonium salt hydrate) to the microdialysis perfusate significantly lowered pre-injury ATP and glutamate levels, and eliminated the post-CCI peaks. Addition of a blocker of store-operated calcium channels [2-aminoethoxy diphenylborinate (2-APB)] to the microdialysis perfusate significantly lowered pre-injury ATP in the hippocampus, and attenuated the post-CCI peak in both the cortex and hippocampus. 2-APB treatment significantly increased baseline glutamate levels, but the values post-injury did not differ from those in the sham group. Pre-injury glucose levels, but not lactate levels, were increased by MRS2179 and decreased by 2-APB. However, none of these treatments substantially altered the CCI-induced reduction in glucose and increase in lactate in the cortex. In conclusion, the results of the present study demonstrated that a short although extensive release of ATP immediately after experimental TBI can be significantly attenuated by blockade of P2Y1 receptors or store-operated calcium channels.

High-dose-infliximab-associated Cerebral Venous Sinus Thrombosis: A Case Report and Review of the Literature.

A 28-year-old woman experienced severe headache and right homonymous hemianopia after receiving high-dose infliximab for Crohn's disease. Computed tomography showed hemorrhagic infarction in the left temporal and parietal lobes. An angiogram revealed left transverse to sigmoid sinus occlusion and a stagnated Labbe vein. The patient was treated surgically and achieved a good outcome. Inflammatory bowel diseases are known to accompany venous and arterial thrombosis in 1-2% of cases. Recently, infliximab has been suggested to increase this possibility. A case of Crohn's disease presenting with cerebral sinus thrombosis in the remission period during long-term/high-dose use of infliximab is presented. In addition, infliximab-associated thrombosis cases were reviewed.

Unusual presentation of a skull base mass lesion in sarcoidosis mimicking malignant neoplasm: a case report.

BACKGROUND: Sarcoidosis is a multi-organ disease of unknown etiology characterised by the presence of epithelioid granulomas, without caseous necrosis. Systemic sarcoidosis is rare among children, while neurosarcoidosis in children is even rarer whether it is systemic or not. CASE PRESENTATION: We described the case of a 12-year-old boy who presented with monocular vision loss accompanied by unusual MRI features of an extensive meningeal infiltrating mass lesion. The patient underwent surgical resection (biopsy) via a frontotemporal craniotomy to establish a definitive diagnosis based on the histopathology, since neurosarcoidosis remains a very difficult diagnosis to establish from neuroradiogenic imagings. Based on the histopathology of the resected mass lesion, neurosarcoidosis was diagnosed. On follow-up after 3 months of steroid therapy, the patient displayed a good response on the imaging studies. MRI revealed that the preexisting mass lesion had regressed extremely. We also conducted a small literature review on imaging studies, manifestations, appropriate treatments, etc., in particular neurosarcoidosis including children. CONCLUSION: Although extremely rare, neurosarcoidosis, even in children, should be considered in the differential diagnosis of skull base mass lesions to avoid unnecessary aggressive surgery and delay in treatment, since surgery may have little role in the treatment of sarcoidosis.

Solitary primary intracranial leptomeningeal glioblastoma invading the normal cortex: Case report.

Solitary primary intracranial leptomeningeal glioma (PLG) is a rare entity of glioma. PLG arises from the heterotopic glial tissue in the subarachnoid space and usually grows there without parenchymal invasion. The present study reported a case of solitary PLG, pathologically diagnosed as glioblastoma, that invaded the temporal cortex and finally disseminated to the spinal cord. A 55-year-old woman had headaches and visited Nihon University, Itabashi Hospital. Head magnetic resonance imaging showed a solid mass mainly located in the right middle fossa extending to the frontal base with strong enhancement effect after contrast medium injection. A conventional angiogram showed a tumor arising from the middle meningeal artery. Fronto-temporal craniotomy was performed to remove the tumor. During reflection of the dura matter, there were numerous small vessels connecting the dura matter and the cortical surface. The tumor was located in the Sylvian fissure and extended around the middle cerebral artery. The border between the tumor and the normal temporal lobe was unclear. Temporal lobectomy was done, but the tumor was left around the perforators of the middle cerebral artery. Hematoxylin and eosin staining showed typical glioblastoma with high cellularity, mitosis, pseudopallisading and vascular proliferation. The tumor cells were immunohistochemically negative for isocitrate dehydrogenase (IDH)1-R132H indicating glioblastoma, IDH-wild type. The patient received chemotherapy and radiation therapy, and was discharged from the hospital. Six months later, local regrowth and spinal dissemination were found. Despite additional chemotherapy and radiation therapy, the tumor became uncontrollable and the patient succumbed. Only 15 cases of solitary PLGs have been reported previously. The IDH status of these tumors have not been investigated in most cases; however, pathological grading varies from lower to higher grade glioma. Together with the pathological difference of astrocytic or oligodendrocytic tumors, solitary PLGs may develop due to various gene alterations similar to intra-axial gliomas.

Pyruvate treatment attenuates cerebral metabolic depression and neuronal loss after experimental traumatic brain injury.

Experimental traumatic brain injury (TBI) is known to produce an acute increase in cerebral glucose utilization, followed rapidly by a generalized cerebral metabolic depression. The current studies determined effects of single or multiple treatments with sodium pyruvate (SP; 1000mg/kg, i.p.) or ethyl pyruvate (EP; 40mg/kg, i.p.) on cerebral glucose metabolism and neuronal injury in rats with unilateral controlled cortical impact (CCI) injury. In Experiment 1 a single treatment was given immediately after CCI. SP significantly improved glucose metabolism in 3 of 13 brain regions while EP improved metabolism in 7 regions compared to saline-treated controls at 24h post-injury. Both SP and EP produced equivalent and significant reductions in dead/dying neurons in cortex and hippocampus at 24h post-CCI. In Experiment 2 SP or EP were administered immediately (time 0) and at 1, 3 and 6h post-CCI. Multiple SP treatments also significantly attenuated TBI-induced reductions in cerebral glucose metabolism (in 4 brain regions) 24h post-CCI, as did multiple injections of EP (in 4 regions). The four pyruvate treatments produced significant neuroprotection in cortex and hippocampus 1day after CCI, similar to that found with a single SP or EP treatment. Thus, early administration of pyruvate compounds enhanced cerebral glucose metabolism and neuronal survival, with 40mg/kg of EP being as effective as 1000mg/kg of SP, and multiple treatments within 6h of injury did not improve upon outcomes seen following a single treatment.

Glucose administration after traumatic brain injury improves cerebral metabolism and reduces secondary neuronal injury.

Clinical studies have indicated an association between acute hyperglycemia and poor outcomes in patients with traumatic brain injury (TBI), although optimal blood glucose levels needed to maximize outcomes for these patients' remain under investigation. Previous results from experimental animal models suggest that post-TBI hyperglycemia may be harmful, neutral, or beneficial. The current studies determined the effects of single or multiple episodes of acute hyperglycemia on cerebral glucose metabolism and neuronal injury in a rodent model of unilateral controlled cortical impact (CCI) injury. In Experiment 1, a single episode of hyperglycemia (50% glucose at 2 g/kg, i.p.) initiated immediately after CCI was found to significantly attenuate a TBI-induced depression of glucose metabolism in cerebral cortex (4 of 6 regions) and subcortical regions (2 of 7) as well as to significantly reduce the number of dead/dying neurons in cortex and hippocampus at 24 h post-CCI. Experiment 2 examined effects of more prolonged and intermittent hyperglycemia induced by glucose administrations (2 g/kg, i.p.) at 0, 1, 3 and 6h post-CCI. The latter study also found significantly improved cerebral metabolism (in 3 of 6 cortical and 3 of 7 subcortical regions) and significant neuroprotection in cortex and hippocampus 1 day after CCI and glucose administration. These results indicate that acute episodes of post-TBI hyperglycemia can be beneficial and are consistent with other recent studies showing benefits of providing exogenous energy substrates during periods of increased cerebral metabolic demand.

Is the circulating plasma volume sufficiently maintained? Fluid management of an aneurysmal subarachnoid hemorrhage in the acute phase.

Cerebral vasospasm is a well-known cause of mortality and morbidity following aneurysmal subarachnoid hemorrhage (SAH). Prevention of symptomatic cerebral vasospasm is the basic management after SAH. Numerous pharmaceutical therapies and endovascular treatments are available against cerebral vasospasm, but none of them have so far proven to improve the outcome. We have focused on maintaining the circulation volume in order to prevent cerebral vasospasm. But to maintain the central venous pressure, huge infusion volume was required, and hyponatremia was frequently observed due to natriuresis and osmotic diuresis. Excessive natriuresis and diuresis cannot be managed through sodium and water replacement, since sodium replacement induces further natriuresis and diuresis (desalination), and water replacement induces hyponatremia. We therefore administered fludrocortisone and hydrocortisone to inhibit excessive natriuresis and diuresis. The efficacy of sodium reabsorption therapy is extremely high to maintain the circulation volume that might have a therapeutic effect to prevent cerebral vasospasm. In this article, we review our institution's experience regarding the management of patients with aneurysmal SAH and also discuss the importance of water and sodium balance when managing such patients.

Delayed sodium pyruvate treatment improves working memory following experimental traumatic brain injury.

Prior work indicates that cerebral glycolysis is impaired following traumatic brain injury (TBI) and that pyruvate treatment acutely after TBI can improve cerebral metabolism and is neuroprotective. Since extracellular levels of glucose decrease during periods of increased cognitive demand and exogenous glucose improves cognitive performance, we hypothesized that pyruvate treatment prior to testing could ameliorate cognitive deficits in rats with TBI. Based on pre-surgical spatial alternation performance in a 4-arm plus-maze, adult male rats were randomized to receive either sham injury or unilateral (left) cortical contusion injury (CCI). On days 4, 9 and 14 after surgery animals received an intraperitoneal injection of either vehicle (Sham-Veh, n=6; CCI-Veh, n=7) or 1000 mg/kg of sodium pyruvate (CCI-SP, n=7). One hour after each injection rats were retested for spatial alternation performance. Animals in the CCI-SP group showed no significant working memory deficits in the spatial alternation task compared to Sham-Veh controls. The percent four/five alternation scores for CCI-Veh rats were significantly decreased from Sham-Veh scores on days 4 and 9 (p<0.01) and from CCI-SP scores on days 4, 9 and 14 (p<0.05). Measures of cortical contusion volume, regional cerebral metabolic rates of glucose and regional cytochrome oxidase activity at day 15 post-injury did not differ between CCI-SP and CCI-Veh groups. These results show that spatial alternation testing can reliably detect temporal deficits and recovery of working memory after TBI and that delayed pyruvate treatment can ameliorate TBI-induced cognitive impairments.

Beneficial effects of sodium or ethyl pyruvate after traumatic brain injury in the rat.

Sodium pyruvate (SP) treatment initiated within 5 min post-injury is neuroprotective in a rat model of unilateral cortical contusion injury (CCI). The current studies examined: (1) effects of delayed SP treatments (1000 mg/kg, i.p., at 1, 12 and 24h), (2) effects of single (1h) or multiple (1, 12 and 24h) ethyl pyruvate treatments (EP; at 20 or 40 mg/kg, i.p.), and (3) mechanisms of action for pyruvate effects after CCI. In Experiment 1, both SP and EP treatment(s) significantly reduced the number of dead/dying cells in the ipsilateral hippocampus (dentate hilus+CA3(c) and/or CA3(a-b) regions) at 72 h post-CCI. Pyruvate treatment(s) attenuated CCI-induced reductions of cerebral cytochrome oxidase activity at 7 2h, significantly improving activity in peri-contusional cortex after multiple SP or EP treatments. Optical density measures of ipsilateral CD11b immuno-staining were significantly increased 72 h post-CCI, but these measures of microglia activation were not different from sham injury values in SP and EP groups with three post-CCI treatments. In Experiment 2, three treatments (1, 12 and 24h) of SP (1000 mg/kg) or EP (40 mg/kg) significantly improved recovery of beam-walking and neurological scores in the first 3 weeks after CCI, and EP treatments significantly improved spatial working memory 1 week post-CCI. Ipsilateral CA3(b) neuronal loss, but not cortical tissue loss, was significantly reduced 1 month post-CCI with pyruvate treatments begun 1h post-CCI. Thus, delayed pyruvate treatments after CCI are neuroprotective and improve neurobehavioral recovery; these effects may be mediated by improved metabolism and reduced inflammation.

Metabolic and histologic effects of sodium pyruvate treatment in the rat after cortical contusion injury.

This study determined the effects of intraperitoneal sodium pyruvate (SP) treatment on the levels of circulating fuels and on cerebral microdialysis levels of glucose (MD(glc)), lactate (MD(lac)), and pyruvate (MD(pyr)), and the effects of SP treatment on neuropathology after left cortical contusion injury (CCI) in rats. SP injection (1000 mg/kg) 5 min after sham injury (Sham-SP) or CCI (CCI-SP) significantly increased arterial pyruvate (p < 0.005) and lactate (p < 0.001) compared to that of saline-treated rats with CCI (CCI-Sal). Serum glucose also increased significantly in CCI-SP compared to that in CCI-Sal rats (p < 0.05), but not in Sham-SP rats. MD(pyr) was not altered after CCI-Sal, whereas MD(lac) levels within the cerebral cortex significantly increased bilaterally (p < 0.05) and those for MD(glc) decreased bilaterally (p < 0.05). MD(pyr) levels increased significantly in both Sham-SP and CCI-SP rats (p < 0.05 vs. CCI-Sal) and were higher in left/injured cortex of the CCI-SP group (p < 0.05 vs. sham-SP). In CCI-SP rats the contralateral MD(lac) decreased below CCI-Sal levels (p < 0.05) and the ipsilateral MD(glc) levels exceeded those of CCI-Sal rats (p < 0.05). Rats with a single low (500 mg/kg) or high dose (1000 mg/kg) SP treatment had fewer damaged cortical cells 6 h post-CCI than did saline-treated rats (p < 0.05), but three hourly injections of SP (1000 mg/kg) were needed to significantly reduce contusion volume 2 weeks after CCI. Thus, a single intraperitoneal SP treatment increases circulating levels of three potential brain fuels, attenuates a CCI-induced reduction in extracellular glucose while increasing extracellular levels of pyruvate, but not lactate, and can attenuate cortical cell damage occurring within 6 h of injury. Enduring (2 week) neuronal protection was achieved only with multiple SP treatments within the first 2 h post-CCI, perhaps reflecting the need for additional fuel throughout the acute period of increased metabolic demands induced by CCI.

Duration of ATP reduction affects extent of CA1 cell death in rat models of fluid percussion injury combined with secondary ischemia.

Secondary ischemia (SI) following traumatic brain injury (TBI) increases damage to the brain in both animals and humans. The current study determined if SI after TBI alters the extent or duration of reduced energy production within the first 24 h post-injury and hippocampal cell loss at one week post-injury. Adult male rats were subjected to sham injury, lateral (LFPI) or central fluid percussion injury (CFPI) only, or to combined LFPI or CFPI with SI. The SI was 8 min of bilateral forebrain ischemia combined with hemorrhagic hypotension, applied at 1 h following FPI. After LFPI alone adenosine triphosphate (ATP) levels within the ipsilateral CA1 were reduced at 2 h (p < 0.05) and subsequently recovered. After LFPI+SI the ATP reductions in CA1 ipsilateral to FPI persisted for 24 h (p < 0.01). ATP levels in the contralateral CA1 were not affected by LFPI alone or LFPI+SI. After CFPI alone CA1 ATP levels were depressed bilaterally only at 2 h (p < 0.05). Similar to the LFPI paradigm, CFPI+SI reduced ATP levels for 24 h (p < 0.01), with bilateral ATP reductions seen after CFPI+SI. Cell counts in the CA1 region at 7 days post-injury revealed no significant neuronal cell loss after LFPI or CFPI alone. Significant neuronal cell loss was present only within the ipsilateral (p < 0.001) CA1 after LFPI+SI, but cell loss was bilateral (p < 0.001) after CFPI+SI. Thus, SI prolongs ATP reductions induced by LFPI and CFPI within the CA1 region and this SI-induced energy reduction appears to adversely affect regional neuronal viability.

Hyponatremia in patients with traumatic brain injury: incidence, mechanism, and response to sodium supplementation or retention therapy with hydrocortisone.

BACKGROUND: Hyponatremia is a frequently observed electrolyte abnormality in patients with central nervous system disease. Several mechanisms, such as SIADH, hypopituitarism, and CSWS, have been proposed with varied incidences among several studies. We attempted to clarify the incidence and mechanism of hyponatremia for each type of TBI. We also assessed the efficacy of sodium supplementation and retention therapy. For sodium retention therapy, hydrocortisone was administered, expecting its mineralocorticoid effect, when the hyponatremia was associated with excess natriuresis. METHODS: Retrospective analysis of 298 patients with TBI between January 2003 and December 2004 was performed. The incidence, background, clinical data, and outcome were evaluated. RESULTS: Of the 298 patients, 50 (16.8%) presented hyponatremia during the time course. Hyponatremia was associated with longer hospital stay (P < .001) and bad outcome (P = .02). Among these 50 patients, 37 recovered from the hyponatremia with simple sodium supplementation. The remaining 13 patients presented massive natriuresis and required additional sodium retention therapy. Hydrocortisone statistically reduced the amount of sodium excretion (P = .002) and returned the serum sodium level to a normal value. CONCLUSIONS: A high rate of hyponatremia after TBI was observed. Further studies are required to establish the precise mechanism of hyponatremia after TBI. Clear definition of CSWS is required to avoid confusion of the pathophysiology that causes hyponatremia. Hydrocortisone was useful to prevent excess natriuresis.

Prediction of symptomatic cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage: relationship to cerebral salt wasting syndrome.

OBJECTIVES: Symptomatic cerebral vasospasm is a major complication in patients with subarachnoid hemorrhage (SAH). Symptomatic cerebral vasospasm has been reported to be related to the patient's blood volume which is influenced by cerebral salt wasting syndrome (CSWS). We undertook a prospective study to assess whether the onset of symptomatic cerebral vasospasm was predictable or not, by observing the phenomena of CSWS (natriuresis and osmotic diuresis). METHODS: Sixty-seven consecutive aneurysmal SAH patients were analysed. After surgery, all patients underwent hypervolemic therapy in order to keep central venous pressure (CVP) within 8-12 cmH(2)O, serum sodium level above 140 mEq/l and a positive water balance. Patients were classified into two groups: those without symptomatic cerebral vasospasm (n=55) and those with symptomatic cerebral vasospasm (n=12). To estimate natriuresis and osmotic diuresis, sodium in/out, water in/out, CVP and other parameters were measured and compared between the two groups. RESULTS: One day before symptomatic cerebral vasospasm, three factors reached statistical difference in the group that experienced symptomatic cerebral vasospasm: sodium balance, urine volume and water balance. On the day of symptomatic cerebral vasospasm, two factors reached statistical difference: sodium excretion and urine volume. No factor was significantly different 2 days before symptomatic cerebral vasospasm. DISCUSSION: Symptomatic cerebral vasospasm has a strong relationship with CSWS. Negative sodium and water balance and increased urine volume indicate a predictor of symptomatic cerebral vasospasm. To predict symptomatic cerebral vasospasm, strict observations are required, because CSWS and symptomatic cerebral vasospasm which follows, develop rapidly.

A randomized controlled trial of hydrocortisone against hyponatremia in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Hyponatremia is common after aneurysmal subarachnoid hemorrhage (SAH). It is caused by natriuresis, which induces osmotic diuresis and decreases blood volume, contributing to symptomatic cerebral vasospasm (SCV). Hypervolemic therapy to prevent SCV will not be efficient under this condition. We conducted a randomized controlled trial to assess the efficacy of hydrocortisone, which promotes sodium retention in the kidneys. METHODS: Seventy-one SAH patients were randomly assigned after surgery to treatment with either a placebo (n=36) or 1200 mg/d of hydrocortisone (n=35) for 10 days and tapered thereafter. Both groups underwent hypervolemic therapy. The primary end point was the prevention of hyponatremia. RESULTS: Hydrocortisone prevented excess sodium excretion (P=0.04) and urine volume (P=0.04). Hydrocortisone maintained the targeted serum sodium level throughout the 14 days (P<0.001), and achieved the management protocol with lower sodium and fluid (P=0.007) supplementation. Hydrocortisone kept the normal plasma osmolarity (P<0.001). SCV occurred in 9 patients (25%) in the placebo group and in 5 (14%) in the hydrocortisone group. No significant difference in the overall outcome was observed between the 2 groups. CONCLUSIONS: Hydrocortisone overcame excess natriuresis and prevented hyponatremia. Although there was no difference in outcome, hydrocortisone supported efficient hypervolemic therapy.

Traumatic cervical internal carotid artery occlusion in an infant. Case report.

A 10-month-old boy presented with traumatic internal carotid artery (ICA) occlusion caused by blunt injury after falling from a baby carrier attached to a standing bicycle. Physical examination found bruises on the scalp in the right temporal region and the right shoulder, but no wound in the neck. Chest radiography showed a right clavicular fracture. He developed left hemiparesis at 19 hours after the injury. Computed tomography revealed cerebral infarct and angiography showed cervical ICA occlusion. Conservative therapy with hemodilution was given under a diagnosis of cervical ICA occlusion caused by extension and rotational head injury. Traumatic cervical ICA occlusion due to blunt injury is not uncommon in adults, but extremely rare in infants. We would like to emphasize the dangers of leaving a baby unattended in a carrier attached to a standing bicycle.

Sagittal magnetic resonance imaging of intramural hematoma from non-traumatic dissection of the anterior cerebral artery. Case report.

A 46-year-old woman presented with non-traumatic anterior cerebral artery dissection manifesting as sudden onset of headache and motor weakness of the right lower limb. Angiography revealed luminal narrowing of the left anterior cerebral artery from the A(3) portion to the distal portion. Sagittal T(1)-weighted magnetic resonance imaging showed hyperintensity due to an intramural hematoma around the flow void signal of the affected anterior cerebral artery. Sagittal magnetic resonance imaging should be performed in suspected cases of anterior cerebral artery dissection to detect the diagnostic finding of intramural hematoma.

Cerebral salt wasting in subarachnoid hemorrhage rats: model, mechanism, and tool.

Cerebral salt wasting (CSW) frequently occurs concomitantly with aneurysmal subarachnoid hemorrhage (SAH). CSW induces excessive natriuresis and osmotic diuresis, and reduces total blood volume. As a result, the risk of symptomatic cerebral vasospasm may be elevated. Therefore, it is important to determine the mechanism of CSW. The purpose of this study was to evaluate whether the rat SAH model exhibits CSW and to investigate the relationship between CSW and natriuretic peptides. A SAH model was produced in 24 rats by perforating a cerebral artery with a nylon thread up through the common carotid artery. To evaluate CSW, urine was cumulatively collected from SAH onset to 12 hours and sodium (Na) excretion was analyzed. Body weight and hematocrit were analyzed before and after SAH onset. Concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in plasma were also analyzed. Urine volume and total Na excretion of SAH rats were significantly higher than those of sham rats (p<0.05). Body weight of SAH rats significantly decreased and hematocrit significantly increased (p < 0.05). ANP concentration was significantly decreased in SAH rats (p<0.05). However, BNP concentrations did not change. This study demonstrated for the first time that a rat SAH model exhibited CSW. It was suggested that the cause of CSW was neither ANP nor BNP. In addition, this rat SAH model will be useful for study of CSW after SAH.