[Show abstract][Hide abstract] ABSTRACT: Delayed cerebral vasospasm is an important pathological feature of subarachnoid hemorrhage (SAH). The cause of vasospasm is multifactorial. Impairs nitric oxide availability and endothelial nitric oxide synthase (eNOS) dysfunction has been reported to underlie vasospasm. Memantine, a low-affinity uncompetitive N-methyl-d-aspartate (NMDA) blocker has been proven to reduce early brain injury after SAH. This study investigated the effect of memantine on attenuation of vasospasm and restoring eNOS functionality. Male Sprague-Dawley rats weighing 350-450 g were randomly divided into three weight-matched groups, sham surgery, SAH + vehicle, and SAH + memantine groups. The effects of memantine on SAH were evaluated by assessing the severity of vasospasm and the expression of eNOS. Memantine effectively ameliorated cerebral vasospasm by restoring eNOS functionality. Memantine can prevent vasospasm in experimental SAH. Treatment strategies may help combat SAH-induced vasospasm in the future.
International Journal of Molecular Sciences 01/2015; 16(6):14171-80. DOI:10.3390/ijms160614171 · 2.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Subarachnoid hemorrhage (SAH) causes brain injury via glutamate excitotoxicity, which leads to an excessive Ca(2+) influx and this starts an apoptotic cascade. Memantine has been proven to reduce brain injury in several types of brain insults. This study investigated the neuro-protective potential of memantine after SAH and explored the underlying mechanisms. An endovascular perforation rat model of SAH was used and Sprague-Dawley rats were randomized into sham surgery, SAH + vehicle, and SAH + memantine groups. The effects of memantine on SAH were evaluated by assessing the neuro-behavioral functions, blood-brain barrier (BBB) permeability and neuronal cell preservation. The mechanisms of action of memantine, with its N-methyl-D-aspartate (NMDA) antagonistic characteristics on nitric oxide synthase (NOS) expression and peroxynitrite formation, were also investigated. The apoptotic cascade after SAH was suppressed by memantine. Neuronal NOS (nNOS) expression, peroxynitrite formation, and subsequent oxidative/nitrosative stress were also reduced. Memantine effectively preserved BBB integrity, rescued neuronal injury, and improved neurological outcome in experimental SAH. Memantine has neuro-protective potential in experimental SAH and may help combat SAH-induced brain damage in the future.
[Show abstract][Hide abstract] ABSTRACT: Aim. Autoimmune rheumatic diseases (ARD) are characterized by systemic inflammation and may affect multiple organs and cause vascular events such as ischemic stroke and acute myocardial infarction. However, the association between ARD and increased risk of dementia is uncertain. This is a retrospective cohort study to investigate and compare the risk of dementia between patients clinically diagnosed with ARD and non-ARD patients during a 5-year follow-up period. Methods. Data were obtained from the Longitudinal Health Insurance Database 2000 (LHID2000). We included 1221 patients receiving ambulatory or hospitalization care and 6105 non-ARD patients; patients were matched by sex, age, and the year of index use of health care. Each patient was studied for 5 years to identify the subsequent manifestation of dementia. The data obtained were analyzed by Cox proportional hazard regression. Results. During the 5-year follow-up period, 30 ARD (2.48%) and 141 non-ARD patients (2.31%) developed dementia. During the 5-year follow-up period, there were no significant differences in the risks of any type of dementia (adjusted hazard ratio (HR), 1.18; 95% CI, 0.79-1.76) in the ARD group after adjusting for demographics and comorbidities. Conclusions. Within the 5-year period, patients with and without ARD were found to have similar risks of developing dementia.
BioMed Research International 04/2014; 2014(2):861812. DOI:10.1155/2014/861812 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several studies have provided evidence with regard to the neuroprotection benefits of hyperbaric oxygen (HBO) therapy in cases of stroke, and HBO also promotes bone marrow stem cells (BMSCs) proliferation and mobilization. This study investigates the influence of HBO therapy on the migration of BMSCs, neurogenesis, gliosis, and inflammation after stroke. Rats that sustained transient middle cerebral artery occlusion (MCAO) were treated with HBO three weeks or two days. The results were examined using a behavior test (modified neurological severity score, mNSS) and immunostaining to evaluate the effects of HBO therapy on migration of BMSCs, neurogenesis, and gliosis, and expression of neurotrophic factors was also evaluated. There was a lower mNSS score in the three-week HBO group when compared with the two-day HBO group. Mobilization of BMSCs to an ischemic area was more improved in long course HBO treatments, suggesting the duration of therapy is crucial for promoting the homing of BMSCs to ischemic brain by HBO therapies. HBO also can stimulate expression of trophic factors and improve neurogenesis and gliosis. These effects may help in neuronal repair after ischemic stroke, and increasing the course of HBO therapy might enhance therapeutic effects on ischemic stroke.
Mediators of Inflammation 02/2013; 2013:512978. DOI:10.1155/2013/512978 · 3.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The relationship between traumatic brain injury (TBI) and the risk of dementia remains controversial. This population based study was designed to estimate and compare the risk of dementia in TBI and non-TBI individuals during the 5 year period after TBI.
This study was a retrospective cohort study. Data were obtained from the Longitudinal Health Insurance Database 2000. We included 44 925 patients receiving ambulatory or hospital care and 224 625 non-TBI patients; patients were matched for sex, age and year of index use of healthcare. Patients <15 years of age and those admitted to the intensive care unit were excluded. Each individual was studied for 5 years to identify the subsequent development of dementia. Data were analysed by Cox proportional hazard regression.
During the 5 year follow-up period, 1196 TBI (2.66%) and 224 625 non-TBI patients (1.53%) patients developed dementia. During the 5 year follow-up period, TBI was independently associated with a 1.68 (range 1.57-1.80) times greater risk of dementia after adjusting for sociodemographic characteristics and selected comorbidities.
The findings of this study suggest an increased risk of dementia among individuals with TBI. We suggest the need for more intensive medical monitoring and health education in individuals with TBI.
Journal of neurology, neurosurgery, and psychiatry 07/2012; 83(11):1080-5. DOI:10.1136/jnnp-2012-302633 · 5.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inflammation, angiogenesis, neurogenesis, and gliosis are involved in traumatic brain injury (TBI). Several studies provide evidence supporting the neuroprotective effect of hyperbaric oxygen (HBO2) therapy in TBI. The aim of this study was to ascertain whether inflammation, angiogenesis, neurogenesis, and gliosis during TBI are affected by HBO2 therapy.
Rats were randomly divided into three groups: TBI + NBA (normobaric air: 21% O2 at 1 absolute atmospheres), TBI + HBO2, and Sham operation + NBA. TBI + HBO2 rats received 100% O2 at 2.0 absolute atmospheres for 1 hr/d for three consecutive days. Behavioral tests and biochemical and histologic evaluations were done 4 days after TBI onset.
TBI + NBA rats displayed: (1) motor and cognitive dysfunction; (2) cerebral infarction and apoptosis; (3) activated inflammation (evidenced by increased brain myeloperoxidase activity and higher serum levels of tumor necrosis factor-α); (4) neuronal loss (evidenced by fewer NeuN-positive cells); and (5) gliosis (evidenced by more glial fibrillary protein-positive cells). In TBI + HBO2 rats, HBO2 therapy significantly reduced TBI-induced motor and cognitive dysfunction, cerebral infarction and apoptosis, activated inflammation, neuronal loss, and gliosis. In addition, HBO2 therapy stimulated angiogenesis (evidenced by more bromodeoxyuridine-positive endothelial and vascular endothelial growth factor-positive cells), neurogenesis (evidenced by more bromodeoxyuridine-NeuN double-positive and glial cells-derived neurotrophic factor-positive cells), and overproduction of interleukin-10 (an anti-inflammatory cytokine).
Collectively, these results suggest that HBO2 therapy may improve outcomes of TBI in rats by inhibiting activated inflammation and gliosis while stimulating both angiogenesis and neurogenesis in the early stage.
[Show abstract][Hide abstract] ABSTRACT: Magnesium sulfate and nimesulide are commonly used drugs with reported neuroprotective effects. Their combination as stroke treatment has the potential benefits of decreasing individual drug dosage and fewer adverse effects. This study evaluated their synergistic effects and compared a low-dose combination with individual drug alone and placebo. Sprague-Dawley rats underwent 90 min of focal ischemia with intraluminal suture occlusion of the middle cerebral artery followed by reperfusion. The rats were randomly assigned to receive one of the following treatments: placebo, magnesium sulfate (MgSO₄; 45 mg/kg) intravenously immediately after the induction of middle cerebral artery occlusion, nimesulide (6 mg/kg) intraperitoneally before reperfusion, and combined therapy. Three days after the ischemia-reperfusion insult, therapeutic outcome was assessed by 2,3,5-triphenyltetrazolium chloride staining and a 28-point neurological severity scoring system. Cyclooxygenase-2, prostaglandin E₂, myeloperoxidase, and caspase-3 expression after treatment were evaluated using Western blot analyses and immunohistochemical staining, followed by immunoreactive cell analysis using tissue cytometry. Only the combination treatment group showed a significant decrease in infarction volume (10.93±6.54% versus 26.43±7.08%, p<0.01), and neurological severity score (p<0.05). Low-dose MgSO₄ or nimesulide showed no significant neuroprotection. There was also significant suppression of cyclooxygenase-2, prostaglandin E₂, myeloperoxidase, and caspase-3 expression in the combination treatment group, suggesting that the combination of the two drugs improved the neuroprotective effects of each individual drug. MgSO₄ and nimesulide have synergistic effects on ischemia-reperfusion insults. Their combination helps decrease drug dosage and adverse effects. Combined treatment strategies may help to combat stroke-induced brain damage in the future.
Journal of neurotrauma 02/2012; 29(7):1518-29. DOI:10.1089/neu.2011.2030 · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: : Heatstroke has been defined as a form of hyperthermia associated with a systemic inflammatory response that leads to multiple organ dysfunction syndrome (MODS). It has also been documented that heat shock protein 70 (HSP70) preconditioning is able to induce thermotolerance. Here, the authors further investigated whether hypobaric hypoxia preconditioning (HHP) improved the MODS in heatstroke by up-regulation of HSP70.
: Anesthetized rats were randomly assigned to (a) non-HHP + nonheated group, (b) non-HHP + heated group, (c) HHP + heated group and (d) HHP + HSP70 antibodies (Abs) + heated groups. All heated groups were exposed to heat stress (43°C, 70 minutes) to induce heatstroke. For HHP, animals were exposed to 0.66 atmosphere absolute (18.3% O2) for 5 hours daily for consecutive 5 days per week for 2 weeks before the start of heat exposure.
: HHP significantly (i) attenuated hypotension, (ii) reduced plasma index of the toxic oxidizing radicals and the organ injury indicator, (iii) attenuated plasma systemic inflammatory response molecules, (iv) reduced an index of infiltration of polymorphonuclear neutrophils in the lung like myeloper-oxidase activity, (v) promoted plasma levels of an anti-inflammatory cytokine, interleukin-10, (vi) promoted the survival time to fourfold compared with non-HHP group and (vii) promoted the overexpression of HSP70 in different organs (eg, the lung) during heatstroke. The beneficial effects of HHP could be significantly attenuated by HSP70 Ab preconditioning.
: Our results show that HHP protects rats from heat-induced MODS via up-regulating HSP70. Thus, HHP could be a novel strategy for the prevention of heatstroke animals or patients before heat exposure.
The American Journal of the Medical Sciences 01/2012; 344(5):383-90. DOI:10.1097/MAJ.0b013e31824314fe · 1.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We evaluated the electrophysiological changes to the cauda equina after low-dose external irradiation in a postlaminotomy fibrosis model in rats.
To clarify the immediate and long-term electrophysiological responses of antifibrotic radiation therapy in a fibrosis model.
Low-dose perioperative radiation therapy inhibits scar formation. However, its efficacy for preventing fibrosis-induced compressive neuropathy and its potential adverse effect on underlying neural structures have not been studied.
Twenty-four rats were placed in 3 groups of 8: group I, sham operation (laminar exposure alone) with a single fraction of 700 cGy external irradiation given using a 9-MeV electron beam 24 hours postsurgery; group II, left L5 hemilaminectomy (laminotomy) alone; and group III, left L5 hemilaminectomy with the same radiation protocol as group 1. We recorded mixed-nerve-elicited somatosensory-evoked potentials (M-SSEP)- and dermal (D)-SSEP at the thoracolumbar junction, and L1-L2 interspinous ligament after percutaneously stimulating the posterior tibial nerve at the bilateral medial ankle and L5 dermatomal fields. We compared the potentials recorded immediately before, 30 minutes, 2 weeks, and 1, 2, and 3 months after surgery on the operated and nonoperated sides. We used gross dissection and histologic sections to evaluate the degree of perineural fibrosis and walking-track analysis for neurologic evaluation.
Pre- and postoperative (30 minutes and 2 weeks) M- and D-SSEP were not statistically different. In group II, the relative amplitude of D-SSEP (elicited from 5 dermatomes) 1, 2, and 3 months postsurgery was lower; however, the M-SSEP in all groups and D-SSEP of groups I and III remained constant. Histologic evaluation of radiation efficacy showed that the frequency and extent of peridural fibrosis was consistently lower in group II than in group III.
Low-dose irradiation reduced peridural fibrosis and prevented fibrosis-induced radiculopathy. The radiation caused no adverse neuropathic complications.
[Show abstract][Hide abstract] ABSTRACT: Orbital tumors are classified as primary and secondary. For primary entities, there are variable pathologies with benign and malignant natures. Many of the orbital tumors should be excised through neurosurgical approaches. We reported 2 cases of orbital tumors, which were clearly disclosed by magnetic resonance imaging.
Case 1 was a 70-year-old woman and case 2 was a 57-year-old woman. Both cases were presented with progressive unilateral proptosis. The pathologies were intraorbital cavernous hemangioma and lacrimal mixed adenoma, respectively. With the scalp incision all posterior to the hairline, frontotemporal orbitozygomatic approach with 1 piece of craniotomy bone flap was performed after freeing all the remaining periorbita and other soft tissue attachments. This approach assures maximum exposure for successful en bloc excisions of these tumors with minimal bone loss, so the cosmetic results are satisfactory.
Even though most orbital tumors are diagnosed by ophthalmologists, most of them should be operated on by neurosurgeons because neurosurgical approaches offer wide and safe surgical windows.
[Show abstract][Hide abstract] ABSTRACT: We report a case with double primary intracranial tumors of different cell types without phacomatosis. The patient was hospitalized due to progressive memory impairment, headaches, dysarthria and right hemiparesis. Initial computed tomographic (CT) examinations revealed a large hyperdense tumor over the right frontal lobe, suggestive of an extra-axial meningioma. Additionally, there was unusual brain edema in the contralateral hemisphere that subsequently proved to originate from an intrinsic tumor. Staged craniotomies were used to treat the patient. Pathological examinations confirmed the two tumors to be a meningioma and a glioblastoma multiforme, respectively. The patient made an uneventful recovery after treatment. Although meningioma and glioma represent two common primary intracranial tumors, the simultaneous development of the two tumors is rare. A randomly occurring event most likely accounted for this linkage in the patient. We suggest that extraordinary brain edema far remote from the primary brain lesion warrants special attention for identifying other potentially undetected lesions.
[Show abstract][Hide abstract] ABSTRACT: Objective: To determine the prognostic factors of the functional outcome of patients surgically treated for acute epidural hematomas. Methods: Two hundred patients who consecutively underwent neurosurgery for acute epidural hematomas over the past 9-year period were studied. Clinical characteristics, radiologic findings, and the time intervals with regard to treatment course were investigated to determine the interactions between all these factors and functional outcome. Results: Functional outcome showed a significant correlation with preoperative consciousness state, Glasgow Coma Scale score, pupillary sizes, and motor posturing (chi(2) test, p < 0.05). Functional outcome correlated with the period of brain hernia tion, the length of time of the operation, as well as the period of hospitalization (chi(2) test, p < 0.05), but not with the length of time of craniotomy decompression relative to the length of time from the injury until admission. The radiologic findings of the associated brain injury, the size and the density of the clot, the degree of the brain shift, and the obliteration of the basal cisterns significantly correlated with functional outcome (chi(2) test, p < 0.05), whereas no significance was attributable to skull fracture. Multivariate analysis indicated that the following four factors independently correlated with functional outcome: (1) associated brain injury, (2) best motor response, (3) hematoma volume, and (4) period of hospitalization (chi(2) test, p < 0.05). A combination of the four factors led to the prediction of the functional outcome with 91% accuracy (1.5% falsely pessimistic predictions and 7.5% falsely optimistic prediction) and 82.1% at over 90% confidence level, These four parameters correlated significantly with preoperative neurologic deterioration (chi(2) test, p < 0.05). Conclusion: This study identifies the risk factors involved in the functional outcome of patients who underwent surgical treatment for acute epidural hematomas, Our results indicate that associated brain injury plus best motor response are the optimal set of two prognostic indicants, with 87% correct predictions and 70.1% at over a 90% confidence level, Prevention of in-hospital neurologic deterioration would improve the patients' functional outcome with a resultant unfavorable recovery rate ranging from 11.5% to 17%.
The Journal of Trauma Injury Infection and Critical Care 11/1998; 45(5):946-952. DOI:10.1097/00005373-199811000-00017