Outcome predictors and clinical presentation of syringomyelia.

BACKGROUND: The prognosis of syringomyelia is not yet established. Syringomyelia derived from different etiologies contributes to similar symptoms. OBJECTIVE: Assess the syringomyelia in our medical institutes and describe the etiologies and clinical appearance of the disorder. And identify the predictors of a good outcome and to find the most suitable timing of surgical intervention according to our results. METHODS: This retrospective cohort study used databases in our hospitals to analyze 70 cases of syringomyelia between 1997 and 2014. All available information was obtained from medical records and radiological reports. We used American Spinal Injuries Association disability scores (ASIA scores), the modified Nurick classification system, and recorded the number of days the patient was hospitalized, for neurological and functional assessment. Univariate and multivariate analyses were used to evaluate the relationship between clinical factors and outcomes. RESULTS: Non-communicating syringomyelia was the most common type of syringomyelia. In univariate analysis, autonomic dysfunction and motor impairment were strong predictors of poor neurological and functional outcomes. In addition to the above factors, syrinxes at the cervical level predicted better functional outcomes than at any spinal level in multivariate analysis. CONCLUSIONS: Motor impairment, which is commonly seen in patients with syringomyelia in Taiwan, is a strong predictor to poor neurological and functional outcomes. Our study indicates that patients without autonomic dysfunction or motor impairment should receive timely surgical intervention to prevent symptomatic deterioration. We also found that cervical syringomyelia in particular has the potential for good functional recovery after adequate intervention.

Real-Time Intraoperative Pressure Monitoring to Avoid Surgically Induced Localized Brain Injury Using a Miniaturized Piezoresistive Pressure Sensor.

Neurosurgical procedures often cause damage to the brain tissue at the periphery from surgical manipulations. Especially during retraction, a large amount of pressure could be applied on the brain surface, which can damage it, leading to brain herniation, which can be fatal for patients. To resolve this issue, we have developed a pressure sensor that can be used to monitor the applied pressure during surgery for intraoperative care. This device was tested on a rodent model to create a superficial surgically induced damage profile for three different applied pressures (30, 50, and 70 mmHg) and compared to a standard intracranial pressure monitoring system. Magnetic resonance imaging has been performed after surgical procedures to detect the herniation caused by applied pressure. To evaluate the damage to brain cells and tissue rupture, histological analysis was performed using hematoxylin and eosin staining. A scoring system was developed to understand the severity of the surgically induced brain injury, which will help neurosurgeons to limit the pressure to an optimum point without causing damage.

Miniaturized Flexible Piezoresistive Pressure Sensors: Poly(3,4-ethylenedioxythiophene):Poly(styrenesulfonate) Copolymers Blended with Graphene Oxide for Biomedical Applications.

Piezoresistive pressure sensors have garnered significant attention because of their wide applications in automobiles, intelligent buildings, and biomedicine. For in vivo testing, the size of pressure sensors is a vital factor to monitor the pressure of specific portions of a human body. Therefore, the primary focus of this study is to miniaturize piezoresistive pressure sensors with graphene oxide (GO)-incorporated poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) composite films on a flexible substrate for biomedical applications. Prior to the fabrication of pressure sensors, a comprehensive material analysis was applied to identify the horizontal placement of GO flakes within the PEDOT:PSS copolymers, revealing a reduction in variable range hopping distance and an enhancement in carrier mobility. For devices scaled to 0.2 cm, the sensitivity of PEDOT:PSS pressure sensors was conspicuously decreased owing to the late response, which can be effectively solved by GO incorporation. Using technology computer-aided design simulations, the current crowded at the PEDOT:PSS film surface and in the vicinity of an indium-tin-oxide electrode corner was found to be responsible for the changes in piezoresistive behaviors of the scaled devices. The miniaturized flexible piezoresistive pressure sensors with PEDOT:PSS/GO composite films are capable of monitoring the brain pressure of intracranial surgery of a rat and discerning different styles of music for a potential application in hearing aids.

Long Term Surgical Outcome and Prognostic Factors of Atypical and Malignant Meningiomas.

Atypical and malignant meningiomas are rare. Our aim was to examine the treatment outcomes following surgical resection, and analyze associations between clinical characteristics and overall survival (OS) or relapse free survival (RFS). 102 patients with atypical or malignant meningiomas underwent microsurgical resection between June 2001 and November 2009 were analyzed retrospectively. We compared demographics, clinical characteristics, treatment, and complications. The five-year and ten-year overall survival rates were 93.5% and 83.4%, respectively. Three factors significantly reduced OS: Malignant meningiomas (p < 0.001), which also decreased RFS (p < 0.001); female patients (p = 0.049), and patients with Karnofsky Performance Status (KPS) < 70 at diagnosis (p = 0.009). Fifty two patients (51%) experienced tumor relapse. Total resection of tumors significantly impacted RFS (p = 0.013). Tumors located at parasagittal and posterior fossa area lead to higher relapse rate (p = 0.004). Subtotal resection without adjuvant radiotherapy lead to the worst local control of tumor (p = 0.030). An MIB-1 index <8% improved OS and RFS (p = 0.003). Total resection of atypical and malignant meningiomas provided better outcome and local control. Adjuvant radiation therapy is indicated for patients with malignant meningiomas, with incompletely excised tumors; or with tumors in the parasagittal or posterior fossa area. The MIB-1 index of the tumor is an independent prognostic factor of clinical outcome.

The Impact of Surgical Experience on Major Intraoperative Aneurysm Rupture and Their Consequences on Outcome: A Multivariate Analysis of 538 Microsurgical Clipping Cases.

The incidence and associated mortality of major intraoperative rupture (MIOR) in intracranial aneurysm surgery is diverse. One possible reason is that many studies failed to consider and properly adjust the factor of surgical experience in the context. We conducted this study to clarify the role of surgical experience on MIOR and associated outcome. 538 consecutive intracranial aneurysm surgeries performed on 501 patients were enrolled in this study. Various potential predictors of MIOR were evaluated with stratified analysis and multivariate logistic regression. The impact of surgical experience and MIOR on outcome was further studied in a logistic regression model with adjustment of each other. The outcome was evaluated using the Glasgow Outcome Scale one year after the surgery. Surgical experience and preoperative Glasgow Coma Scale (GCS) were identified as independent predictors of MIOR. Experienced neurovascular surgeons encountered fewer cases of MIOR compared to novice neurosurgeons (MIOR, 18/225, 8.0% vs. 50/313, 16.0%, P = 0.009). Inexperience and MIOR were both associated with a worse outcome. Compared to experienced neurovascular surgeons, inexperienced neurosurgeons had a 1.90-fold risk of poor outcome. On the other hand, MIOR resulted in a 3.21-fold risk of unfavorable outcome compared to those without it. Those MIOR cases managed by experienced neurovascular surgeons had a better prognosis compared with those managed by inexperienced neurosurgeons (poor outcome, 4/18, 22% vs. 30/50, 60%, P = 0.013).

Corpus callosum involvement and postoperative outcomes of patients with gliomas.

Corpus callosum involvement is associated with poorer survival in high grade glioma (HGG), but the prognostic value in low grade glioma (LGG) is unclear. To determine the prognostic impact of corpus callosum involvement on progression free survival (PFS) and overall survival (OS) in HGG and LGG, the records of 233 glioma patients treated from 2008 to 2011 were retrospectively reviewed. Preoperative magnetic resonance (MR) images were used to identify corpus callosum involvement. Age, sex, preoperative Karnofsky performance scale, postoperative Eastern Cooperative Oncology Group (ECOG) score and extent of resection (EOR) were evaluated with respect to PFS and OS. The incidence of corpus callosum involvement was similar among HGG (14 %) and LGG (14.5 %). Univariate analysis revealed that PFS and OS were significantly shorter in both WHO grade II and grade IV glioma with corpus callosum involvement (both, p < 0.05). Multivariate analysis showed that grade II glioma with corpus callosum involvement have shorter PFS (p = 0.03), while EOR, instead of corpus callosum involvement (p = 0.16), was an independent factor associated with PFS in grade IV glioma (p < 0.05). Corpus callosum involvement was no longer significantly associated with OS after adjusting age, gender, EOR, preoperative and postoperative performance status (p = 0.16, 0.17 and 0.56 in grade II, III and IV gliomas, respectively). Corpus callosum involvement happened in both LGG and HGG, and is associated with lower EOR and higher postoperative ECOG score both in LGG and HGG. Corpus callosum involvement tends to be an independent prognostic factor for PFS in LGG, but not for OS in LGG or in HGG.

Skull base atypical meningioma: long term surgical outcome and prognostic factors.

PURPOSE: The aim of this study was to examine the clinical outcomes of treating atypical meningioma at the skull base region following surgical resection and adjuvant radiotherapy, and to analyze the association between clinical characteristics and progression free survival. MATERIALS AND METHODS: Twenty-eight patients with skull base atypical meningiomas underwent microsurgical resection between June 2001 and November 2009. The clinical characteristics of the patients and meningiomas, the extent of surgical resection, and complications after treatment were retrospectively analyzed. RESULTS: Thirteen patients (46.4%) had disease recurrence or progression during follow up time. The median time to disease progression was 64 months. The extent of the surgical resection significantly impacted prognosis. Gross total resection (GTR) of the tumor improved progression free survival (PFS) compared to subtotal resection (STR, p = 0.011). An older patient age at diagnosis also resulted in a worse outcome (p = 0.024). An MIB-1 index <8% also contributed to improved PFS (p = 0.031). None of the patients that underwent GTR and received adjuvant radiotherapy had tumors recur during follow up. STR with adjuvant radiotherapy tended to result in better local tumor control than STR alone (p = 0.074). Three of 28 patients (10.7%) developed complications after microsurgery. The GTR group had a higher rate of complications than those with STR. There were no late adverse effects after adjuvant radiotherapy during follow up. CONCLUSION: For patients with skull base atypical meningiomas, GTR is desirable for longer PFS, unless radical excision is expected to lead to severe complications. Adjuvant radiation therapy is advisable to reduce tumor recurrence regardless of the extent of surgical resection. Age of disease onset and the MIB-1 index of the tumor were both independent prognostic factors of clinical outcome.

Adult supratentorial extra-pineal primitive neuro-ectodermal tumors.

Primitive neuro-ectodermal tumors (PNET) are rare malignant brain tumors, mostly undifferentiated, that tend to spread through the cerebrospinal fluid (CSF). Extra-pineal supratentorial PNET in adults are very rare. Published guidelines for adult PNET were not available until 2011, and at our institute surgeons and oncologists did not have consensus on imaging evaluation or treatment protocols between 1994 to 2008. Twenty-two consecutive adult patients with extra-pineal supratentorial PNET from this period were reviewed in this retrospective study. Their clinical profiles and radiologic images were evaluated. A pathological review based on the 2007 World Health Organization criteria was also conducted. Prognostic factors were analyzed. The 1 and 3 year overall survival rates were 64% and 32% for adult extra-pineal supratentorial PNET, respectively. Limited by the small number of tumors in this series, we suggest that negative prognostic factors are multiplicity at onset, initial CSF seeding, and tumor differentiation. Although age of onset, extent of resection, radiation and chemotherapy were assumed to be good prognostic factors, the analysis did not reveal strong significance for overall survival with univariate and multivariate analysis. We believe more detailed investigations on the genetic/molecular basis of supratentorial PNET and their clinical outcomes are warranted.

Fractionated stereotactic radiosurgery using the Novalis system for the management of pituitary adenomas close to the optic apparatus.

Radiosurgery has been proven to be an effective treatment for residual or recurrent pituitary adenomas after surgery. However, it causes severe complications when the optic apparatus is irradiated over the tolerance dose. In this study, we analyzed the feasibility of fractionated stereotactic radiosurgery to treat pituitary tumors close to the optic apparatus. Thirty-four patients from June 2006 to June 2011 with recurrent or residual pituitary adenomas close to (<3 mm) the optic apparatus were treated with fractionated stereotactic radiosurgery. Three fractions with a total dose of 2100 cGy were applied to the tumors. Imaging, examination of vision, and estimation of hormone level were regularly performed before and after radiosurgery. The mean tumor volume before fractioned stereotactic radiosurgery was 5.06±3.08 cm3 (range: 0.82-12.69 cm3). After a mean follow up of 36.8±15.7 months (range: 16-72 months), tumor size was reduced in seven (20.6%) patients and remained the same in the other 27 (79.4%) patients. Vision was improved in one patient and remained stable in the rest. Only one patient developed transient post-treatment diplopia. This study suggests that fractionated stereotactic radiosurgery is safe for treating pituitary adenomas close to the optic apparatus. Studies with more patients and longer follow-up are required to draw definite conclusions.

Brain surgery in patients with liver cirrhosis.

OBJECT: Liver cirrhosis was identified as an independent predictor of poor outcomes in patients suffering trauma and in those undergoing major surgeries. The aim of this study was to report the authors' experiences treating patients with cirrhosis who undergo brain surgeries. METHODS: Between 2004 and 2009, 121 consecutive patients with cirrhosis underwent 144 brain procedures. Patients were categorized as Child-Turcotte-Pugh (referred to as "Child") Class A, B, or C. The patient profiles, including the severity of cirrhosis, reason for surgery, complications, and prognosis factors, were analyzed. RESULTS: In this retrospective study, the overall surgical complication rate for patients with cirrhosis was 52.1% and the mortality rate was 24.3%. For patients with acute traumatic brain injury (TBI), the complication, rebleeding, and mortality rates reached 84.4%, 68.8%, and 37.5%, respectively. Surgery for TBI was a significant risk factor for postoperative complications (p = 0.0002) and postoperative hemorrhage (p < 0.0001). Otherwise, according to the Child classification, the complication rate increased in a stepwise fashion from 38.7% to 60% to 84.2%, the rebleeding rate from 29.3% to 48.0% to 63.2%, and the mortality rate from 5.3% to 38% to 63.2% for Child A, B, and C, respectively. The Child classification was associated with higher risk of complications-Child B vs A OR 2.84 (95% CI 1.28-6.29), Child C vs A OR 5.39 (95% CI 1.32-22.02). It was also associated with risk of death-Child C vs A OR 30.43 (95% CI 7.71-120.02), Child B vs A OR 10.88 (95% CI 3.42-34.63). CONCLUSIONS: Liver cirrhosis is a poor comorbidity factor for brain surgery. The authors' results suggest that the Child classification used independently is a poor prognostic factor; in addition, grave outcomes were observed in patients with TBI.

A chip-based method for studying the effects of exogenous proteins on neuronal axons.

Axons are long, slender processes of neurons that have various functions at different stages of development. Here, we report the use of a chip device to study the effects of various exogenous proteins on the growth and presynaptic differentiation of axons in a high-throughput manner. The device consists of a glass chip whose surface contains a protein-coated micropattern. When neurons are maintained on the chip, a specific region of the chip surface will be occupied exclusively by axons. The axons and clusters of release-competent synaptic vesicles, a presynapse-like specialization in the axon, can be quantified as the proportions of this specific region's area occupied respectively by these subcellular structures. By using chips with this specific region coated with different proteins, these proteins' effects on the growth and presynaptic differentiation of the axon were investigated by comparing the amounts of axons and clusters of release-competent synaptic vesicles in this region of the chip. We also demonstrate another application of this chip device by investigating the effective range of the signal produced by the interaction between neurons and neuroligin 1 in neurons. These results indicate the diverse applications of the chip device in exploring various issues pertaining to axonal functions.

Minimally invasive decompression with posterior column reinforcement for the treatment of symptomatic osteoporotic fracture with spinal stenosis in lumbar vertebrae.

An osteoporotic fracture (OF) in the second to fifth lumbar vertebrae with spinal stenosis may be an indication for surgical treatment, but carries the risks of instability or instrumentation failure. Modified surgical procedures have been developed to manage patients with challenging OF. We retrospectively studied 12 patients (three male, nine female; mean age±standard deviation=73.5±7.2 years) who underwent minimally invasive decompression and posterior column reinforcement with polymethylmethacrylate. During a mean follow-up period of 24.8±3.1 months, pain severity and functional impairment were both significantly reduced, as measured by the visual analog scale and the Oswestry disability index. Nine patients (75%) experienced a satisfactory outcome while the other three (25%) were unchanged. Plain radiographs showed stable spinal alignment and immobilization of flexion-extension within the PMMA construct. Five complications were managed successfully, including one by revision surgery. These procedures are a feasible surgical option in the elderly population studied.

Comparison of the kinematic features between the in vivo active and passive flexion-extension of the subaxial cervical spine and their biomechanical implications.

STUDY DESIGN: An in vivo motion analysis of active and passive kinematic cervical flexion-extension. OBJECTIVE: The study was aimed at investigating the differences between the active and passive kinematic sagittal motions of the subaxial cervical spine. SUMMARY OF BACKGROUND DATA: The biomechanical behavior of the cadaver spinal column is different from that of the in vivo spine. Two major issues were concerned: the complex neuromuscular control of the in vivo cervical spinal motion and the unknown true nature of the passive cervical spinal motion. The kinematic characteristics of active and passive spinal motions need to be clarified. METHODS: The active and passive motion patterns of the subaxial spine in the sagittal plane were recorded by digital video fluoroscopy. The motion of functional units from C3-C4 to C6-C7 of the cervical spine were processed using Image J, an image processing software, in both active and passive cervical motions. The Cobb's angle was measured in serial flexion and extension motions, and a comparison of this angle in both active and passive motions was made in 12 patients with degenerative disc herniation. RESULTS: The difference between active and passive gentle flexion was minimal, and the degree of their correlation was high. The differences in the degree of gentle extension between active and passive motion were variable, and their correlation was low. During early passive flexion, the degree of flexion at the upper level was less and that at the lower level was more as compared to that observed at the respective levels in early active flexion. CONCLUSION: In gentle flexion, the active and passive cervical spinal motions are closely approximated, which implies that the active neuromuscular control mainly plays the buffer-and-brake mechanism without placing additional load on the spine. In contrast, the degree of passive extension is limited, and active neuromuscular control may place additional load on the spine.

Outcomes of 75 patients over 12 years treated for acoustic neuromas with linear accelerator-based radiosurgery.

The aim of this study was to investigate the efficacy of linear accelerator (LINAC)-based radiosurgery in the treatment of acoustic neuromas. In this retrospective study, we enrolled 75 patients with non-neurofibromatosis type 2 acoustic neuromas who were followed-up for more than 5years. The 75 patients were divided into 3 groups: patients with a newly diagnosed tumor; those with a residual tumor; and those with a recurrent tumor. The average follow-up period was 97.8months. The overall tumor progression-free rate was 92%, and corresponding rates among those with newly diagnosed tumors was 100%, residual tumors was 84.4%, and recurrent tumors was 92.8% (p=0.028). Lesion localization using CT scans correlated with a higher tendency for tumor progression than lesion localization using CT-MRI fusion images (15.6% versus 2.4%, respectively). Residual tumors treated with radiosurgery have a higher progression rate, and careful lesion localization using CT-MRI image fusion is required.

Stereotactic brain biopsy: Single center retrospective analysis of complications.

OBJECTIVE: Stereotactic biopsy is a widely used surgical technique for the histological diagnosis of intracranial lesions. Potential risks of this procedure, such as hemorrhage, seizure, and infection have been established, and different risk factors have been characterized. However, these risks have been addressed by only few studies conducted in Asian countries. MATERIALS AND METHODS: The study group is comprised of 299 consecutive stereotactic biopsy procedures by 11 neurosurgeons between 2004 and 2007. The pre-operative medical conditions, methods of biopsy and postoperative complications were analyzed. RESULT: The overall diagnostic yield was 90.64%. Complications were observed in 7.36% of the cases, with symptomatic hemorrhages occurring in 4.35% of the cases, and the overall mortality rate in this study population was 1.34%. Patients with liver cirrhosis were at a higher risk of hemorrhage. Other clinical, radiological, or histological variables were not associated with an increased risk of complications. CONCLUSION: Stereotactic brain biopsy is a safe and reliable way to obtain a histological diagnosis. Based on our recent clinical experiences, the data suggests that more attention should be paid to liver cirrhotic patients, since the chance on hemorrhage is significantly larger.

The plastic surgeon's role in extracranial-to-intracranial bypass using a reverse great saphenous vein graft.

BACKGROUND: Extracranial-to-intracranial bypass is used for flow replacement and diversion that prevent the serious complications associated with sudden ligation of the middle cerebral artery for treatment of complex tumors or aneurysms. Extracranial-to-intracranial bypass is a demanding procedure that requires experience in advanced microsurgical techniques. In this article, the authors review the first report of an extracranial-to-intracranial bypass performed by a plastic surgeon with emphasis on indications for microsurgical involvement in neurosurgical practice and on description of the surgical technique. METHODS: Between April of 2004 and October of 2006, three extracranial-to-intracranial bypass cases were performed including one for a complex aneurysm rupture and two for resections of cranial base tumors. In every case, the intracranial approach was used by the neurosurgeon. The bypass was performed by interposing a reverse great saphenous vein graft between the superficial temporal artery, in end-to-end anastomosis, and the second segment of the middle cerebral artery, in end-to-side anastomosis. RESULTS: In each case, postoperative cerebral angiography demonstrated complete patency of the extracranial-to-intracranial bypass. Neither of the two surviving patients at a mean follow-up of 13 months had deterioration of neurologic function, postoperative stroke, or surgery-related death. One of the patients was dead before the 6-month follow-up. CONCLUSIONS: The reverse great saphenous vein graft is a good option for extracranial-to-intracranial bypass, with the advantages of high-flow graft, wide lumen, adequate length, easy harvest, and minimal donor-site morbidity. The plastic surgery/neurosurgery alliance allows scope for improved outcomes in complex neurosurgical cases and continues to push the frontiers of reconstructive microsurgery.

Hypoglossal schwannoma presenting as hemi-atrophy of the tongue.

Schwannoma of the hypoglossal nerve is extremely rare. We report the clinical manifestations of a patient with Schwannoma of the hypoglossal nerve with hemi-atrophy of the tongue and numbness in the lip. Magnetic resonance image study of the brain showed a lobulated mass at the right posterior fossa with an extension to the right upper neck. Surgical intervention was performed with right occipital craniotomy and a partial resection of C1 and occipital condyle. Pathological studies confirmed a Schwannoma with hemorrhages and necrosis.

Dexamethasone enhances upregulation of nerve growth factor mRNA expression in ischemic rat brain.

Nerve growth factor (NGF) is well-established as a trophic factor that plays a crucial role in neuroregeneration and plasticity after brain insults. Dexamethasone (DEX), a powerful glucocorticoid steroid, has long been used in the clinical management of neurological disorders. We examined the relationship between NGF and DEX after an ischemic insult to the brain. In situ hybridization was used to measure NGF mRNA expression in the rat hippocampus after 20 min of transient forebrain ischemia. Immunostaining for NGF protein was performed using the avidin-biotin peroxidase method. Immunohistochemistry for glial fibrillary acidic protein (GFAP) was also used to study the astrocyte reaction in the hippocampal CA1 area. Ischemic brain from rats not treated with DEX had a 2 and 3 fold increase in NGF mRNA compared to sham-operated rats at 4 and 6 h after ischemia, respectively. The NGF mRNA expression returned to basal levels 12 h to 7 days post-ischemia. Treatment with DEX potentiated the ischemia-induced increase of NGF mRNA to 4 times that of sham-operated rats at 6 h following reperfusion and NGF protein expression was similarly elevated. Additionally, the number of GFAP positive astrocytes in the CA1 region in the ischemic rats was markedly increased. These data suggest that DEX may play a role in modulating NGF mRNA expression in the hippocampal neuronal response to brain ischemia.

Effect of dexamethasone on the expression of brain-derived neurotrophic factor and neurotrophin-3 messenger ribonucleic acids after forebrain ischemia in the rat.

OBJECTIVE: To determine whether a large dose of dexamethasone affected brain damage induced by concurrent cerebral ischemia, we used in situ hybridization to examine the expression of brain-derived neurotrophic factor and neurotrophin-3 messenger ribonucleic acids (mRNAs) in rats with and without dexamethasone administration after transient forebrain ischemia. DESIGN: Prospective experimental study in rats. SETTING: Experimental laboratory in a teaching hospital and university. SUBJECTS: Eighty adult rats. INTERVENTIONS: Twenty minutes of transient forebrain ischemia was induced by occlusion of four vessels in lightly anesthetized rats. Thirty-six animals received dexamethasone (15 mg/kg, intraperitoneally) after initial reperfusion. Thirty-six dexamethasone-control rats were injected with saline, and the remaining animals underwent sham surgery but no ischemia or dexamethasone. MEASUREMENTS AND MAIN RESULTS: Using in situ hybridization, we determined hippocampal brain-derived neurotrophic factor and neurotrophin-3 mRNA expression 2, 4, 6, 12, and 24 hrs and 2, 3, 4, and 7 days after brain ischemia. Additionally, hippocampal CA1 region cell death was measured with Nissl stains. Both brain-derived neurotrophic factor and neurotrophin-3 mRNA exhibited a biphasic response after ischemia. Brain-derived neurotrophic factor mRNA showed two peaks of 4.07-fold and 2.84-fold increases relative to sham operation at 6 hrs and 2 days, respectively. Neurotrophin-3 mRNA initially decreased to 59% of sham levels at 4 hrs and then increased to 146% at 3 days before it returned to basal levels. When the ischemic rats were treated with dexamethasone, the elevation of brain-derived neurotrophic factor mRNA and the reduction of neurotrophin-3 mRNA level were prevented within the first 24 hrs, and hippocampal CA1 neurons were protected from ischemia-induced cell loss 7 days after brain ischemia. The protein levels of both brain-derived neurotrophic factor and neurotrophin-3 in general correspond to the mRNA levels in the hippocampal region. CONCLUSIONS: Dexamethasone modulates the intriguing temporal and spatial expression of brain-derived neurotrophic factor and neurotrophin-3 that predominantly supports neuronal innervation at different times after brain ischemia and also may provide specific trophic support for various neurons in the central nervous system.