Cerebral vasospasm and hypoperfusion after traumatic brain injury: Combined CT angiography and CT perfusion imaging study.

BACKGROUND: Timely identification of the cerebral perfusion abnormalities after traumatic brain injury (TBI) is highly important. The objective of this study was the evaluation of the post traumatic vasospasm and cerebral hypoperfusion with the serial combined CT angiography (CTA) and CT perfusion (CTP) imaging examinations. METHODS: The case series comprised 25 adult patients with closed TBI accompanied by various types of intracranial hematoma. Emergency surgery was done in 15 cases (60%). Combined CTA and CTP were performed on days 0 (D0) and 7 ± 1 (D7) after trauma. RESULTS: CTA on D0 did not demonstrate vasospasm in any case but revealed it on D7 in 9 patients (36%). In the multivariate analysis, only the presence of subarachnoid hemorrhage (SAH) on D7 had confirmed a significant association with the development of vasospasm (P = 0.0201). Cerebral hypoperfusion at least in one evaluated brain region was noted on D0 and D7 in 76% and 60% of patients, respectively, and showed highly variable spatial distribution and temporal development. Treatment results were not associated with the presence of vasospasm (P = 0.7337) or the number of brain regions affected by hypoperfusion on D0 (P = 0.2285), but the number of brain regions affected by hypoperfusion on D7 was significantly greater in cases of unfavorable outcome (P = 0.0187). CONCLUSION: Vasospasm is merely related to SAH sustained at the subacute stage of TBI, but its spatial and temporary interrelationships with the post traumatic cerebral hypoperfusion are complex. Serial combined CTA and CTP examinations may facilitate monitoring of perfusion abnormalities and treatment guidance.

Twelve-year single critical care center experience of nicardipine prolonged-release implants in patients with subarachnoid hemorrhage: a propensity score matching analysis.

OBJECTIVE: To develop a nicardipine prolonged-release implant (NPRI) to prevent cerebral vasospasm in patients with subarachnoid hemorrhage in 1999, which may be used during craniotomy, and report the results of our recent 12-year single critical care center experience. METHODS: Of 432 patients with aneurysmal subarachnoid hemorrhage treated between 2007 and 2019, 291 were enrolled. 97 Patients were aged >70 years (33%), 194 were female (67%), 138 were World Federation of Neurological Societies grades 1, 2, and 3 (47%), 218 were Fisher group 3 (75%), and 243 had an anterior circulation aneurysm (84%). Using a propensity score matching method for these five factors, the severity of cerebral vasospasm, occurrence of delayed cerebral infarction, and modified Rankin Scale (mRS) score at discharge were analyzed. RESULTS: One hundred patients each with or without NPRI were selected, and the ratios of coil/clip were 0/100 and 88/12, respectively. Cerebral vasospasm and delayed cerebral infarction were both significantly less common in the NPRI group (p=0.004, OR=0.412 (95% CI 0.223 to 0.760) and p=0.005, OR=0.272 (95% CI 0.103 to 0.714, respectively); a significant difference was seen in the mRS score at discharge by Fisher's exact test (p=0.0025). A mRS score of 6 (dead) was less common in the group with NPRI, and mRS scores of 0 and 1 were also less common. No side effects were seen. CONCLUSIONS: NPRIs significantly reduced the occurrence of cerebral vasospasm and delayed cerebral infraction without any side effects. The NPRI and non-NPRI groups showed different patterns of short-term outcomes in the single critical care center, which might have been due to selection bias and patient characteristics. Differences in outcomes may become clear in comparisons with patients treated by craniotomy.

[A Case of Segmental Arterial Mediolysis:Subarachnoid Hemorrhage Followed by Abdominal Bleeding].

We describe a case involving subarachnoid and intraperitoneal hemorrhage due to segmental arterial mediolysis(SAM). A 77-year-old female patient with sudden subarachnoid hemorrhage was immediately transferred to our institution. The hemorrhage was classified as grade 2 according to the World Federation of Neurosurgical Societies system. The patient was a non-smoker and did not drink alcohol regularly. A right internal carotid aneurysm was detected using CT angiography and was clipped during frontotemporal craniotomy. Bleeding was observed from the anterior wall of the internal carotid artery, and the tear was clipped. The patient had an uneventful postoperative course until sudden cardiopulmonary arrest eight days after craniotomy. She died of massive intraperitoneal hemorrhage. Autopsy revealed that the hemorrhage was due to dissection of the celiac artery. Tunica media denaturation was observed not only in the celiac artery, but also in the splenic and internal carotid arteries, which exhibited ruptured aneurysms, and the patient was diagnosed with segmental arterial mediolysis(SAM). SAM is an arterial degenerative disease affecting the medial layer of the arterial and dissecting walls. Multiple lesions are sometimes found. Radiographic imaging findings of SAM are similar to those of dissecting aneurysms, which are characterized by a single continuous dissection of the medial layer. As observed in this case, abdominal bleeding caused by SAM can occur after intracranial bleeding. When surgeons encounter unusual intracranial dissecting aneurysms, SAM should be considered as a differential diagnosis.

Disturbance of CT perfusion within 24 h after onset is associated with WFNS grade but not development of DCI in patients with aneurysmal SAH.

BACKGROUND: Delayed cerebral ischemia (DCI) is a serious complication following aneurysmal SAH (aSAH) and remains a leading cause of morbidity and mortality. We investigated whether data from CT perfusion (CTP) within 24 h after onset are associated with DCI and its outcome. METHODS: We retrospectively examined plain CT, CTP, and CT angiography (CTA) of aSAH patients on arrival. We measured the average mean transit time (aMTT) and compared it with several clinical factors, such as the age, WFNS grade, Fisher group, delayed cerebral infarction, cerebral vasospasm, and modified Rankin scale (mRS), at 1 month. Regions of interest (ROIs) were quantitatively determined in cortical and two basal ganglia areas. RESULTS: Delayed cerebral ischemia (DCI) developed in 11 patients and cerebral vasospasm in 28 patients out of a total of 86 aSAH patients scanned within 24 h after onset. The average MTT was correlated with the WFNS grade (p = 0.000), but not mRS (p = 0.128), age (p = 0.759), DCI (p = 0.669), or cerebral vasospasm (p = 0.306). On the other hand, DCI was associated with the Fisher group (p = 0.0056), mRS (p = 0.0052), and cerebral vasospasm (p = 0.000). Moreover, there were no significant differences in the average MTT within 24 h after onset between territories with and without DCI, or between patients with and without DCI. CONCLUSIONS: The current findings suggest that disturbance of CT perfusion soon after the onset is associated with the WFNS grade but not with the development of DCI. Delayed cerebral ischemia may be solely caused by cerebral vasospasm due to a clot in the cistern, but not associated with early brain injury.

Nonspastic hemifacial spasm confirmed by abnormal muscle responses.

BACKGROUND: Hemifacial spasm is usually diagnosed by inspection which mainly identifies involuntary movements of orbicularis oculi. Assessing abnormal muscle responses (AMR) is another diagnostic method. CASE DESCRIPTION: We report a case of left hemifacial spasm without detectable involuntary facial movements. The patient was a 48-year-old man with a long history of subjective left facial twitching. On magnetic resonance imaging (MRI), the left VIIth cranial nerve was compressed by the left anterior inferior cerebellar artery (AICA), which was in turn compressed by the left vertebral artery. We initially treated him with botulinum toxin. We were able to record AMR, and hemifacial spasm occurred after AMR stimulation, although no spasm was detectable by inspection. Subsequently, we performed microvascular decompression with transposition of the AICA that compressed the VIIth cranial nerve. His hemifacial spasm resolved by 5 weeks after surgery and was not induced by AMR stimulation. CONCLUSION: Hemifacial spasm can sometimes be diagnosed by detecting AMR rather than by visual inspection. We propose that such hemifacial spasm should be termed nonspastic hemifacial spasm.

[Radiation-Induced Malignant Peripheral Nerve Sheath Tumor of the High Cervical Spine].

UNLABELLED: CASE: A 30-year-old woman presented with posterior cervical pain and left-sided omalgia. The patient had a history of non-Hodgkin's lymphoma for which she had received prophylactic whole-brain irradiation(including at the upper cervical level)17 years previously. A magnetic resonance imaging(MRI)scan obtained 1 month previously showed an intradural extramedullary mass lesion at the left C1/2 level. We initially considered the tumor to be a benign schwannoma, but the patient subsequently developed left hemiparesis and was consequently admitted 2 days after her first visit. A second MRI scan showed that the tumor had progressed markedly. Hence, the patient underwent emergency surgical excision of the tumor. However, the tumor could only be partially removed because it had strongly adhered to the ventral aspect of the spinal cord. The tumor was pathologically diagnosed as a malignant peripheral nerve sheath tumor(MPNST). The residual tumor was subjected to local irradiation and surgery, but the treatment was unsuccessful, and the patient died on the 91st day of her illness. Conclusion:We report a case of radiation-induced high cervical MPNST arising from a benign schwannoma. All 9 previously reported cases of radiation-induced spinal MPNST were reviewed. Intraspinal MPNST of the high cervical region are extremely rare and are associated with a very poor prognosis. The 5-year survival rate of such tumors is markedly worse than that of other types of MPNST, and no standard treatment has been established for this condition.

Prognostic Assessment of Aneurysmal Subarachnoid Patients with WFNS Grade V by CT Perfusion on Arrival.

BACKGROUND: The prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH) depends on their condition on arrival at the hospital. However, a small number of patients recover from an initially poor condition. We investigated the correlation between quantitative measures of computed tomography (CT) perfusion (CTP) on arrival and the outcomes of patients with World Federation of Neurosurgical Society (WFNS) grade V aSAH. METHODS: We performed plain CT, CTP, and CT angiography (CTA) in all patients with aSAH on arrival. Aneurysms were surgically obliterated in patients with stable vital signs and the presence of a brain stem response. We measured the average mean transit time (aMTT) and compared it with the modified Rankin Scale (mRS) score at 1 month. Regions of interest were identified as 24 areas in the bilateral anterior, middle, and posterior cerebral artery territories and 2 areas in the basal ganglia. RESULTS: A total of 57 patients were treated between 2007 and 2014. None of the 21 patients with aMTT >6.385 seconds achieved a favorable outcome, whereas 8 of the 36 patients with aMTT <6.385 seconds did achieve a favorable outcome (P = 0.015). Furthermore, comparing the number of areas showing a mean transit time (MTT) >7.0 seconds among the aforementioned 8 areas and mRS, favorable outcomes were not seen in 24 patients with more than 2 such areas (P = 0.009). CONCLUSION: We cannot expect a favorable outcome for patients with WFNS grade V aSAH with aMTT >6.385 seconds or more than 2 of 8 areas with MTT >7.0 seconds.

[Clinical features of bilateral trigeminal neuralgia].

Among 238 patients with bilateral trigeminal neuralgia(TN)who visited our hospital between April 2007 and June 2014, 5(2%)were surgically treated by microvascular decompression(MVD). The initial symptom was on the right side in four and on both sides in one patient. Intervals between the initial and second onset on the other side(left)were two months, and four, six, and eight years. None of the patients showed involvement of the first branch of the trigeminal nerve. The patients with bilateral TN were younger than the 154 patients with unilateral TN who were treated surgically by MVD in this period(45 vs. 65 years), and the bilateral TN patients predominantly were women(4/5 vs. 99/154). In the surgical field, the trigeminal nerve and root entry zone were compressed more by veins in the bi lateral TN patients than in the unilateral TN(4/5 vs. 60/154, respectively)patients. We could not identify any differences in MRI CISS before versus after the onset of left trigeminal neuralgia, suggesting that compression is not the sole cause of the symptom.

[Immediate improvement of ischemic oculopathy after stenting for internal carotid artery stenosis].

Ocular ischemic syndrome occurs when ocular circulation becomes impaired owing to various causes, leading to disturbances in the visual function. It ultimately progresses to neovascular glaucoma and loss of sight. Therefore, the early diagnosis and treatment of patients with ocular ischemic syndrome has a major effect on their visual prognosis. Herein, we describe a patient who complained of decreased vision in one eye. The patient was subsequently diagnosed with internal carotid artery stenosis because of neovascularity (rubeosis iridis) around the iris in the anterior eye. The vision of the patient improved immediately after carotid artery stenting. A review of the literature indicated that the visual improvement could be attributed to the reversal of retrograde blood flow, caused by internal carotid artery stenosis, to normal levels; the resolution of rubeosis in the anterior eye; and improvement in the visual field constriction.

[Trigeminal neuralgia caused by cerebellopontine angle lipoma:a case report and review of the literature].

A 59-year-old man presented with right trigeminal neuralgia of the second branch, which had been treated with carbamazepine. The pain could not be controlled adequately because of side effects. CT and MRI revealed a 2-cm lesion in the right cerebellopontine angle. Retrosigmoid lateral suboccipital craniectomy was performed, and a soft yellowish mass was found to be associated with the 5th, 7th, and 8th cranial nerves, anterior inferior cerebellar artery, and small vessels. The lipoma was partially resected from around the root entry zone(REZ)of the 5th nerve and small vessels were coagulated around the REZ. After surgery, there was no trigeminal neuralgia, but facial numbness and cerebellar signs were noted. Postoperative MRI showed decompression of the trigeminal nerve and venous infarction in the middle cerebellar peduncle. Reviewing similar cases, we found 19 lipoma patients presenting with trigeminal neuralgia. Symptoms of involvement of other cranial nerves were also present in 11 patients, and 14 were younger than 30 years old. Of 17 surgical cases, total resection was not attempted apart from one case. Although pain relief was achieved in all surgical cases, complications developed in 11. Surgery should be performed only in patients with disabling and uncontrolled symptoms.

[A case of acute aortic dissection presenting with cerebral ischemic symptoms: utility of 3D CT angiography and CT perfusion for the diagnosis of acute stroke].

A 76-year-old woman presented at our hospital complaining of loss of consciousness, dysarthria, and upper extremity paresis. Head CT showed no remarkable findings. 3D CT angiography (CTA) and CT perfusion (CTP) revealed acute aortic dissection (AAD) involving the innominate artery and decreased cerebral blood flow in the right cerebral hemisphere, although there were no clinical signs of AAD. The patient underwent emergency allograft replacement performed by cardiovascular surgeons. The symptoms disappeared within several days and no cerebral infarction developed. Although patients with AAD and neurological symptoms can show a fatal course when they receive tissue plasminogen activator (tPA), it is difficult to exclude patient with AAD as candidates for tPA treatment. Routine use of 3D CTA and CTP in the diagnosis of acute stroke may help overcome the above problem.

Sensitivity of CT perfusion for the diagnosis of cerebral infarction.

We aimed to determine the sensitivity of CT perfusion (CTP) for the diagnosis of cerebral infarction in the acute stage. We retrospectively reviewed patients with ischemic stroke who underwent brain CTP on arrival and MRI-diffusion weighted image (DWI) after hospitalization between October 2008 and October 2011. Final diagnosis was made from MRI-DWI findings and 87 patients were identified. Fifty-five out of 87 patients (63%) could be diagnosed with cerebral infarction by initial CTP. The sensitivity depends on the area size (s): 29% for S < 3 cm(2), 83% for S ≥ 3 cm(2) - < 6 cm(2), 88% for S ≥ 6 cm(2) - < 9 cm(2), 80% for S ≥ 9 cm(2) - < 12 cm(2), and 96% for S ≥ 12 cm(2) (p < 0.001). Sensitivity depends on the type of infarction: 0% for lacunar, 74% for atherothrombotic, and 92% for cardioembolism (p < 0.001). Sensitivity is not correlated with hours after onset. CT perfusion is an effective imaging modality for the diagnosis and treatment decisions for acute stroke, particularly more serious strokes.

[A case of cavernous sinus epidermoid: anatomical classification and surgical approach].

Epidermoid rarely appears in the cavernous sinus. We encountered a 41-year-old man with left abducens nerve palsy. A round-shaped, low-density lesion on CT was located lateral to the left cavernous sinus with a compressed and thinned lateral wall of the sphenoid sinus. We could not identify cranial nerves in the cavernous sinus, which was found to be packed with a non-enhanced, high-intensity tumor on both T1 and T2 MRI. Part of the tumor capsule and its pearly contents were removed with an intradural subtemporal approach, and an inner membranous layer with cranial nerves and a tumor capsule were seen at the bottom of the tumor cavity. Postoperatively, complete cure was achieved. Reviewing similar cases, we found 18 cavernous sinus epidermoids:extracavernous type in 5;interdural in 10;and intracavernous in 3. The interdural type could be further divided into two subtypes:superficial cavernous sinus and inner membranous types. The present case belongs to the former. Frontotemporal and subtemporal procedures via both intra- and extradural approaches are relatively safe for lesions except for the intracavernous type, because cranial nerves are not located in the lateral wall of the tumor. MRI provides more useful information on cranial nerves and aid in choosing a better treatment strategy.

[A case of intraventricular meningioma manifesting akinetic mutism after complicated management of hydrocephalus].

A 26-year-old male with large intraventricular meningioma developed acute hydrocephalus postoperatively, which was difficult to manage. After a repeated course of dilated and slit-like ventricle, he gradually presented a disturbance of consciousness, which was recovered by the use of bromocriptine, suggesting akinetic mutism. At the chronic stage, he suffered from symptoms of hydrocephalus again. Time-slip MRI revealed the stasis of CSF flow around the third ventricle. Neuroendoscopy disclosed that the foramen of Monro was occluded with membrane. After endoscopic third ventriculostomy as well as penetration of the foramen, the symptoms disappeared and hydrocephalus was resolved. This is a rare case of akinetic mutism after complicated management of hydrocephalus associated with intraventricular meningioma.

Gene expression in a canine basilar artery vasospasm model: a genome-wide network-based analysis.

To investigate the changes of gene expression on the cerebral vasospasm after subarachnoid hemorrhage, we used genome-wide microarray for a canine double-hemorrhage model and analyzed the data by using a network-based analysis. Six dogs were assigned to two groups of three animals: control and hemorrhage. The effects were assessed by the changes in gene expressions in the artery 7 days after the first blood injection. Among 23,914 genes, 447 and 66 genes were up-regulated more than two- and fivefold, respectively, and 332 and 25 genes were down-regulated more than two- and fivefold, respectively. According to gene ontology, genes related to cell communication (P = 5.28E-10), host-pathogen interaction (7.65E-8), and defense-immunity protein activity (0.000183) were significantly overrepresented. The top high-level function for the merged network derived from the network-based analysis was cell signaling, revealing that the subgroup that regulates the quantity of Ca(2+) to have the strongest association significance (P = 4.75E-16). Canine microarray analysis followed by gene ontology profiling and connectivity analysis identified several functional groups and individual genes responding to cerebral vasospasm. Ca(2+) regulation may play a key role in these gene expression changes and may be involved in the pathogenesis of cerebral vasospasm.

Increased expression of ephrin A1 in brain arteriovenous malformation: DNA microarray analysis.

A number of previous studies have revealed the abnormal expression of various angiogenesis-related genes or products in brain arteriovenous malformation (AVM). To understand the molecular process of this disease, we analyzed gene expression profiles in brain AVM. Using a DNA microarray consisting of 17,086 genes, we identified differentially expressed genes in 5 brain AVMs from their draining veins, vessels retaining basic venous architecture. Not many genes were differentially expressed between the AVM nidus and the draining vein. When we applied an absolute cut-off value for normalized log2 (cy5/cy3 ratio) of 0.4, 19 genes were selected. Genes such as SOX8, TRIM2, FENA1 (ephrin A1), and AQP4 were upregulated, and genes such as I_1000105, KRT18, IGFBP7, EMILIN-2, and KRT14 were downregulated. Genes relating to angiogenesis, such as vascular endothelial growth factor and angiopoietin and other members of the ephrin family, were not differentiated. Among differentially expressed genes detected in this analysis, we focused on ephrin A1, a gene related to embryogenesis and angiogenesis. The expression of ephrin A1 was two and three to nine times higher than that of the draining vein and normal brain, respectively, using real-time reverse transcription-polymerase chain reaction. For the first time, here we report the increased expression of ephrin A1 in brain AVM, which may play an important role in the pathogenesis of AVM.

Application of nicardipine prolonged-release implants: analysis of 97 consecutive patients with acute subarachnoid hemorrhage.

OBJECTIVE: Since October 1999, nicardipine prolonged-release implants (NPRIs) have been used to prevent vasospasm in patients with subarachnoid hemorrhage. This study was conducted to examine the incidence of cerebral vasospasm and outcome after the application of NPRIs. METHODS: Ninety-seven consecutive patients among 125 patients with subarachnoid hemorrhage who were surgically treated within 72 hours were analyzed. NPRIs were applied principally to patients with thick clots (Fisher Group 3) through a frontotemporal or frontal craniotomy. Sixty-nine patients, including five in Fisher Group 2, were treated with NPRIs, and 28 were not. NPRIs were placed in the cisterns of thick clots where vasospasm was highly probable. RESULTS: Four (6%) of the 69 patients treated with NPRIs and 3 (11%) of the 28 patients not treated with NPRIs developed delayed ischemic neurological deficits (DINDs). Of these patients, clinical deterioration with infarction occurred in two patients (3%). Current smoking (P = 0.0088) and intraventricular hemorrhage on admission computed tomographic (CT) scans (P = 0.0077) were correlated with DIND. CT groupings on admission and postoperatively were not correlated, nor were World Federation of Neurosurgical Societies grades. Hypertension was inversely correlated with DIND (P = 0.0233). Eighty-six patients (89%) had an independent status at 3 months. Logistic regression analysis demonstrated that age (odds ratio [OR], 6.836; P = 0.034), World Federation of Neurosurgical Societies grade (OR, 23.317; P = 0.001), intraventricular hemorrhage on admission CT scans (OR, 6.332; P = 0.024), and surgical complications (OR, 32.861; P = 0.003) were independent risk factors influencing an unfavorable outcome. CT grouping on admission and DIND were not. CONCLUSION: Our findings suggest that the incidence of DIND may decrease and, therefore, an unfavorable outcome may improve if NPRIs are applied for patients with thick clots (Fisher Group 3) during surgery.

Influence of endothelial nitric oxide synthase T-786C single nucleotide polymorphism on aneurysm size.

OBJECT: Among patients with aneurysms, those with heterozygous (T/C) endothelial nitric oxide synthase (eNOS) T-786C single nucleotide polymorphism (SNP), a mutation reducing endothelial nitric oxide synthesis, are reported to have larger ruptured intracranial aneurysms (IAs) than those with homozygous (C/C or T/T) genotype. The authors tested patients harboring aneurysms for eNOS T-786C SNP in two populations--Japanese and Korean. METHODS: The eNOS T-786C SNP was genotyped through direct sequencing in genomic DNA obtained from 336 Japanese and 191 Korean patients with lAs and 214 Japanese and 191 Korean control volunteers. Differences in genotype frequencies among the various aneurysm sizes were evaluated using the Fisher exact test. There was no significant difference in heterozygous (T/C) eNOS T-786C SNP between aneurysms 5 mm or smaller and those from 6 to 9 mm, and between lesions 5 mm or smaller and those 10 mm or larger in 336 Japanese patients harboring aneurysms--220 with ruptured and 116 with unruptured lesions--and in 191 Korean patients with ruptured aneurysms. CONCLUSION: The eNOS T-786C SNP genotype does not influence the size of aneurysms.

Role of p38 mitogen-activated protein kinase on cerebral vasospasm after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Inflammatory cytokines are involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was conducted to examine the role of p38 mitogen-activated protein kinase (MAPK) in the development of vasospasm and cytokine production. METHODS: We measured the expression levels of genes and proteins related to inflammation in human vascular smooth muscle cells (hVSMCs) treated with hemolysate and FR167653 (FR) (1 micromol/L), a selective p38MAPK inhibitor, for 48 hours by TaqMan real-time reverse transcription-polymerase chain reaction (RT-PCR) and ELISA. Twenty-one dogs were assigned to 3 groups of 7 animals: control, placebo, and FR-treated (1 mg/kg/d) groups in a double-hemorrhage model. The effects were assessed through the caliber of the basilar artery, and the changes in gene expressions and the activation of p38MAPK were assessed by Western blot analysis. RESULTS: Treatment of hVSMCs with hemolysate induced significant upregulation of interleukin (IL)-1alpha, IL-1beta, and IL-8 gene and protein expressions, which was suppressed significantly with FR. The mean vessel caliber on day 7, as a percentage of that of day 0, was 49% in the placebo, and 74% in the FR group (P=0.0001). The gene expression levels of IL-1alpha, IL-1beta, and IL-8 in the arterial wall were extremely elevated in the placebo, and significantly suppressed in the FR group (P=0.0027, 0.0002, and 0.0073). p38MAPK phosphorylation was stimulated in the placebo and hemolysate in vitro, and suppressed in the FR group. CONCLUSIONS: These results suggest that p38MAPK is activated in the arterial wall after SAH, leading to the development of vasospasm, possibly through the upregulation of inflammatory cytokines.