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PubMedDate not supplied

Results of whole brain radiation therapy in patients with brain metastases from colorectal carcinoma.

AIMS AND BACKGROUND: Carcinoma of the colon-rectum is an infrequent cause of brain metastases, constituting 1.5% of all metastatic lesions to the brain. We reviewed our experience in the treatment of brain metastases from colorectal cancer to define the efficacy of whole brain radiation therapy as a palliative measure in this setting of patients. METHODS: Twenty-three consecutive cases of brain metastasis from colorectal cancer treated between 1999 and 2004 were identified in the files of the Division of Radiotherapy of the A Businco Regional Oncological Hospital, Cagliari. Their records were reviewed for patient and tumor characteristics and categorized according to the RTOG RPA classes. RESULTS: Fifteen patients (65%) had multiple metastases. Twenty-one patients (91%) showed extracranial metastases. Fourteen patients were classified as RTOG RPA class II and 9 class III. The median radiation dose delivered was 2000 cGy in 5 fractions in one week (range, 20-36 Gy). In 14 of 20 assessable patients (70%), symptomatic improvement was observed. The median follow-up and survival time for all the patients, 12 females and 11 males, was 3 months. In 3 patients only the cause of death was the brain metastasis. CONCLUSIONS: Despite the disappointing survival time, external radiation therapy to the whole brain proved to be an efficacious palliative treatment for patients with multiple or inoperable brain metastasis from colorectal cancer.

Adult↗
PubMed2006

Whole brain radiation therapy in management of brain metastasis: results and prognostic factors.

PURPOSE: To evaluate the prognostic factors associated with overall survival in patients with brain metastasis treated with whole brain radiotherapy (WBRT) and estimate the potential improvement in survival for patients with brain metastases, stratified by the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class. PATIENTS AND METHODS: From January 1996 to December 2000, 270 medical records of patients with diagnosis of brain metastasis, who received WBRT in the Hospital do Cancer Sao Paulo A.C. Camargo in the period, were analyzed. The surgery followed by WBRT was used in 15% of patients and 85% of others patients were submitted at WBRT alone; in this cohort 134 patients (50%) received the fractionation schedule of 30 Gy in 10 fractions. The most common primary tumor type was breast (33%) followed by lung (29%), and solitary brain metastasis was present in 38.1% of patients. The prognostic factors evaluated for overall survival were: gender, age, Karnofsky Performance Status (KPS), number of lesions, localization of lesions, primary tumor site, surgery, chemotherapy, absence extracranial disease, RPA class and radiation doses and fractionation. RESULTS: The OS in 1, 2 and 3 years was 25.1%, 10.4% and 4.3% respectively, and the median survival time was 4.6 months. The median survival time in months according to RPA class after WBRT was: 6.2 class I, 4.2 class II and 3.0 class III (p < 0.0001). In univariate analysis, the significant prognostic factors associated with better survival were: KPS higher than 70 (p < 0.0001), neurosurgery (p < 0.0001) and solitary brain metastasis (p = 0.009). In multivariate analysis, KPS higher than 70 (p < 0.001) and neurosurgery (p = 0.001) maintained positively associated with the survival. CONCLUSION: In this series, the patients with higher perform status, RPA class I, and treated with surgery followed by whole brain radiotherapy had better survival. This data suggest that patients with cancer and a single metastasis to the brain may be treated effectively with surgical resection plus radiotherapy. The different radiotherapy doses and fractionation schedules did not altered survival.

Adult↗
PubMed2002

Brain atrophy in multiple sclerosis: impact of lesions and of damage of whole brain tissue.

INTRODUCTION: In multiple sclerosis (MS), brain atrophy measurement on magnetic resonance imaging (MRI) reflects overall tissue loss, especially demyelination and axonal loss. We studied which factor contributes most to the development of brain atrophy extent and severity of lesions or damage of whole brain issue (WBT). METHODS: Eighty-six patients with MS [32 primary progressive (PP), 32 secondary progressive (SP)] and 22 relapsing-remitting (RR) were studied MRI included T1- and T2-weighted imaging to obtain hypointense T1 lesion volume (T1LV) and two brain volume measurements: 1) the parenchymal fraction (PF; whole brain parenchymal volume/intracranial volume) as a marker of overall brain volume, and 2) the ventricular fraction (VF; ventricular volume/intracranial volume) as a marker of central atrophy. From magnetization transfer ratio (MTR) histograms, the relative peak height (rHp) was derived as an index of damage of WBT (a lower peak height reflects damage of WBT). RESULTS: Multiple linear regression analysis revealed that damage of WBT explains most of the variance of PF (standardized coeffcient beta = 0.59, p < 0.001 for WBT and beta = -0.19, p < 0.05 for T1LV). These findings are independent of disease phase; even in RR patients, damage of WBT plays a dominant role in explaining the variance in overall brain volume. By contrast the variance in VF is explained by both T1LV and damage of WBT (standardized coefficient beta = 0.43, p < 0.001 for T1LV and beta =-0.38, p < 0.001 for WBT). CONCLUSION: This study shows that overall brain volume (PF) is best explained by damage of WBT, supporting the significance of nonfocal pathology in MS in producing tissue loss. Central atrophy (VP) is determined by both lesion volume and damage of WBT. Our results underline the importance of nonfocal pathology even in the early (RR) phase of the disease.

Adult↗
PubMed2006

The brain tumor gene negatively regulates neural progenitor cell proliferation in the larval central brain of Drosophila.

Brain development in Drosophila is characterized by two neurogenic periods, one during embryogenesis and a second during larval life. Although much is known about embryonic neurogenesis, little is known about the genetic control of postembryonic brain development. Here we use mosaic analysis with a repressible cell marker (MARCM) to study the role of the brain tumor (brat) gene in neural proliferation control and tumour suppression in postembryonic brain development of Drosophila. Our findings indicate that overproliferation in brat mutants is due to loss of proliferation control in the larval central brain and not in the optic lobe. Clonal analysis indicates that the brat mutation affects cell proliferation in a cell-autonomous manner and cell cycle marker expression shows that cells of brat mutant clones show uncontrolled proliferation, which persists into adulthood. Analysis of the expression of molecular markers, which characterize cell types in wild-type neural lineages, indicates that brat mutant clones comprise an excessive number of cells, which have molecular features of undifferentiated progenitor cells that lack nuclear Prospero (Pros). pros mutant clones phenocopy brat mutant clones in the larval central brain, and targeted expression of wild-type pros in brat mutant clones promotes cell cycle exit and differentiation of brat mutant cells, thereby abrogating brain tumour formation. Taken together, our results provide evidence that the tumour suppressor brat negatively regulates cell proliferation during larval central brain development of Drosophila, and suggest that Prospero acts as a key downstream effector of brat in cell fate specification and proliferation control.

Animals↗
PubMed2005

Binding of the positron emission tomography tracer Pittsburgh compound-B reflects the amount of amyloid-beta in Alzheimer's disease brain but not in transgenic mouse brain.

During the development of in vivo amyloid imaging agents, an effort was made to use micro-positron emission tomography (PET) imaging in the presenilin-1 (PS1)/amyloid precursor protein (APP) transgenic mouse model of CNS amyloid deposition to screen new compounds and further study Pittsburgh Compound-B (PIB), a PET tracer that has been shown to be retained well in amyloid-containing areas of Alzheimer's disease (AD) brain. Unexpectedly, we saw no significant retention of PIB in this model even at 12 months of age when amyloid deposition in the PS1/APP mouse typically exceeds that seen in AD. This study describes a series of ex vivo and postmortem in vitro studies designed to explain this low retention. Ex vivo brain pharmacokinetic studies confirmed the low in vivo PIB retention observed in micro-PET experiments. In vitro binding studies showed that PS1/APP brain tissue contained less than one high-affinity (K(d) = 1-2 nm) PIB binding site per 1000 molecules of amyloid-beta (Abeta), whereas AD brain contained >500 PIB binding sites per 1000 molecules of Abeta. Synthetic Abeta closely resembled PS1/APP brain in having less than one high-affinity PIB binding site per 1000 molecules of Abeta, although the characteristics of the few high-affinity PIB binding sites found on synthetic Abeta were very similar to those found in AD brain. We hypothesize that differences in the time course of deposition or tissue factors present during deposition lead to differences in secondary structure between Abeta deposited in AD brain and either synthetic Abeta or Abeta deposited in PS1/APP brain.

Alzheimer Disease↗
PubMed2000

[Changes in brain metabolites under combined mild-hypothermia and isoflurane anesthesia in rat with temporal brain ischemia].

The significance of mild-hypothermia as a treatment of brain ischemia-induced neuronal cell death was investigated by measurement of hippocampul excitatory amino acids, brain lactate and energy-charge just after 10 min of transient forebrain ischemia in a rat model with four vessels occluded. After 10 min of ischemia, cerebral circulation was restored. At that time, in the control group transient increases of hippocampul aspartate and glutamic acid levels were observed. Furthermore, brain lactate levels were also elevated but the energy-charge was reduced. These significant changes were observed in the non-isoflurane anesthesia and mild-hypothermia rats (control group). However, in rats with treatment of either isoflurane or mild-hypothermia, the excessive amount of amino acids and the significant fluctuation of brain metabolic/energy pathway seen in the control group were suppressed. Particularly, in the combined treatment group, these increased and decreased phenomena induced by brain ischemia were significantly inhibited. In a group of pre- and post-treatment of mild-hypothermia, the maximum peak of lactate was significantly less than that seen in the control group, although the sustained increased level of lactate was detected. These results indicate that the combined treatment with isoflurane anesthesia and mild-hypothermia is a suitable treatment for the brain dysfunction induced by ischemia and that the sustained hypothermia may help restore brain lactate levels after brain ischemia because of the lasting anaerobic metabolism.

Anesthesia, Inhalation↗
PubMed1975

[Abscess of the brain (2nd report)--special reference to surgical indication of extracapsular excision of brain abscess (author's transl)].

Brain abscess persists as a serious diagnostic problem and critical therapeutic challenge since pre-antibiotic era. After antibiotic agents has been introduced, abscess of the brain seems to be a surgical curable intracranial suppurative disease, although surgical mortality and morbidity due to brain abscess are still distressingly high. Recently, the incidence of brain abscess are gradually increasing. In this present situation, it is necessary to reevaluate the previous method and surgical results of brain abscess. Even with new surgical techniques and antibiotics, the mortality rate and number of neurological deficits remain high, as previously methods, it is most important how to eliminate these problems. It was undertaken to determine the significant factors affecting the clinical management of patients with this serious problem. The general outlines of our neurosurgical treatment are given, with emphasis on our surgical schedule of brain abscess, especially brain abscess in congenital heart disease. In this paper, a review of the current status of the surgical methods, operative mortality and morbidity, diagnostic methods and the therapy of brain abscess has been discussed.

Adolescent↗
PubMed2000

[Effect of baicalin and dexamethasone on cytokines in brain tissue of infectious brain edema].

OBJECTIVE: To explore the effect of baicalin(BC) and dexamethasone(DXM) on interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha(TNF-alpha) in brain tissues of infectious brain edema. METHODS: The infectious brain edema model induced by pertussis bacilli(PB) was used. Brain water content(WC), content of Na+ and the levels of IL-1 beta, TNF-alpha were determined, and the morphological changes were observed under the light microscope. RESULTS: The results showed that the levels of WC, Na+, IL-1 beta and TNF-alpha in group PB were higher than those in group of normal saline(NS) (P < 0.01). And they were lower in groups BC and DXM than those in group PB(P < 0.05). In groups BC and DXM, there were no significant difference in the contents of water, Na+, IL-1 beta and TNF-alpha(P > 0.05). The water contents were positive linar correlated with IL-1 beta or TNF-alpha(P > 0.05). The water contents were positive linear correlated with IL-1 beta or TNF-alpha contents(r = 0.9381, 0.8349, P < 0.01). The structure of brain tissues in group NS was normal. In group PB, there were severe edema in brain tissues. In groups BC and DXM, the edema of brain tissues was reduced. CONCLUSIONS: The results suggest that the protective effect of BC and DXM against infectious brain edema were similar, the mechanism may be associated with the reduction of TNF-alpha and IL-1 beta.

Animals↗
PubMed2003

Role of endogenous regucalcin in brain function: suppression of cytosolic nitric oxide synthase and nuclear protein tyrosine phosphatase activities in brain tissue of transgenic rats.

The role of regucalcin, a regulatory protein of Ca2+ signaling, in the regulation of brain function was investigated by using regucalcin transgenic (TG) rats. Western blot analysis showed a remarkable expression of regucalcin protein in the cytosol and nucleus of the brain tissue of TG female rats (5-week-old) as compared with that of wild-type (wt) female rats. In TG male rats, the enhancement of regucalcin expression in the brain cytosol and nucleus was only slight. Nitric oxide (NO) synthase activity was significantly decreased in the brain cytosol of TG female rats. Protein tyrosine phosphatase activity was not significantly altered in the brain nucleus of TG female rats. The presence of calcium chloride (10 microM) or anti-regucalcin monoclonal antibody (50 ng/ml) in the enzyme reaction mixture caused a significant increase in cytosolic NO synthase and nuclear protein tyrosine phosphatase activities in the brain tissue of wt rats. The increase was significantly prevented in the brain cytosol and nucleus of TG rats. The present study supports the view that endogenous regucalcin plays a suppressive role in the regulation of brain function in rats.

Animals↗
PubMed2004

[Sequential treatment of VmP regimen and whole brain radiotherapy for small cell lung cancer patients with brain metastases].

BACKGROUND & OBJECTIVE: Median survival time (MST) of small cell lung cancer (SCLC) patients with brain metastases was short when patients were palliatively treated with either chemotherapy or whole brain radiotherapy (WBRT). This study was designed to compare therapeutic effects,toxicities,and survival time of 2 different sequential treatments of VmP regimen and WBRT for SCLC patients with brain metastases. METHODS: According to bed availability, 38 naive SCLC patients with brain metastases were nonrandomized into group A and group B. There was no significant difference of characteristics between 2 groups (Chi-s Fisher's exact test, P >0.05). Patients in group A (VmP-WBRT) received 2 cycles of VmP regimen (teniposide, 60 mg/m(2),d(1-5), cisplatin, 25 mg/m(2), d(1-3), repeated every 4 weeks),and then WBRT (3 Gy x 10,within 2 weeks); patients in group B (WBRT-VmP) received the same WBRT in advance,and then 2 cycles of VmP regimen. Patients with single brain lesion received an extra 3 Gy x 5 radiotherapy on the limited field of brain lesion within 1 week after WBRT. All patients received 2-4 cycles of chemotherapy after sequential treatments. RESULTS: Both sequential treatments relieved neurological symptoms of more than 80% of patients. Response rates of brain,lung,and total lesions of group A and B had no significant differences (68.2% vs. 75.0%, P=0.647; 77.3% vs. 75%, P=0.871; 63.6% vs. 56.3%, P=0.646,respectively). Time to progression (TTP) of group A was 6.0 (95% CI 4.4-7.6) months,of group B was 5.0 (95% CI 3.6-6.4) months (P=0.383). MST of group A was 12.0 (95% CI 7.9-16.1) months,of group B was 9.0 (95% CI 5.6-12.4) months (P=0.049). One-year survival rate of group A was 31.8%,of group B was 18.8% (P=0.281),and 2-year survival rates were 13.6%, and 6.3% (P=0.844). Myelosuppression was the main concentration-dependent toxicity. Incidence of vomit at stage III in group B was higher than that in group A (P=0.01). All treatment toxicities were tolerable and manageable. CONCLUSION: Both sequential treatments can be safely performed for SCLC patients with brain metastases, may relieve neurological symptoms, and well control both primary and metastatic lesions. VmP-WBRT sequential treatment may prolong survival time of SCLC patients for 3 months.

Adult↗
PubMed1992

[Treatment of metastatic brain tumors: effect of surgery of multiple metastatic brain tumors and systemic metastasis with special reference to quality of life].

To assess the efficacy of surgical resection of brain metastases from patients with multiple brain metastases or/and with other systemic metastases, the authors analysed treatment results of 90 cases of metastatic brain tumors. The patients were divided into three groups. Group A (nine cases): Patients with single brain tumor and their primary cancers were well controlled. Their brain tumors were removed surgically and followed by radiation. Their mean survival time was 17.0 months, and 14.6 months were independent (Karnofsky score greater than or equal to 70) in cases of lung cancer. Five patients (55.6%) improved by treatment. Group B (21 cases): Patients with multiple brain metastases or/and with systemic metastases. Their brain tumor(s) which gave rise to neurological symptoms were surgically removed in order to improve their quality of life. In cases of lung cancer, mean survival time was 9.5 months and 7.1 months were independent. 11 patients (52.3%) improved by treatment. Group C (60 cases): Patients treated conservatively. Their mean survival time was 4.9 months and 2.7 months were independent in cases of lung cancer. Only 13 patients (21.7%) improved by treatment. However 23 (38.3%) deteriorated in their quality of life during treatment. Two patients of this group had single brain tumor and their primary cancers were controlled well. They refused surgery. Their mean survival time was 13.0 months, and 7.0 months were independent. These times were statistically shorter than group A. Seven patients had similar systemic and neurological states as those in group B. Their mean survival time was 5.0 months and 3.0 months were independent. These times were also statistically shorter than those in group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Neoplasms↗
PubMed2006

New protein extraction/solubilization protocol for gel-based proteomics of rat (female) whole brain and brain regions.

The rat is an accepted model for studying human psychiatric/neurological disorders. We provide a protocol for total soluble protein extraction using trichloroacetic acid/acetone (TCA/A) from rat (female) whole brain, 10 brain regions and the pituitary gland, and show that two-dimensional gel electrophoresis (2-DGE) using pre-cast immobilized pH (4-7) gradient (IPG) strip gels (13 cm) in the first dimension yields clean silver nitrate stained protein profiles. Though TCA/A precipitation may not be "ideal", the important choice here is the selection of an appropriate lysis buffer (LB) for solubilizing precipitated proteins. Our results reveal enrichment of protein spots by use of individual brain regions rather than whole brain, as well as the presence of differentially expressed spots in their proteomes. Thus individual brain regions provide improved protein coverage and are better suited for differential protein detection. Moreover, using a phosphoprotein-specific dye, in-gel detection of phosphoproteins was demonstrated. Representative high-resolution silver nitrate stained proteome profiles of rat whole brain total soluble protein are presented. Shortcomings apart (failure to separate membrane proteins), gel-based proteomics remains a viable option, and 2-DGE is the method of choice for generating high-resolution proteome maps of rat brain and brain regions.

Animals↗
PubMed1984

Assessment of the functional role of brain adrenergic neurons: chronic effects of phenylethanolamine N-methyltransferase inhibitors and alpha adrenergic receptor antagonists on brain norepinephrine metabolism.

The potential role of brain adrenergic neurons in regulating noradrenergic neuronal metabolism was assessed using inhibitors of phenylethanolamine N-methyltransferase (PNMT), the enzyme responsible for epinephrine production. Two centrally active PNMT inhibitors (SK&F 64139 and LY134046) were administered over a 6-day treatment period to cause prolonged reductions in epinephrine formation. In brain regions containing endogenous epinephrine (medulla-pons and hypothalamus), chronic treatment with PNMT inhibitors produced: 1) reductions of epinephrine content, 2) elevation of tyrosine hydroxylase activity and 3) elevation of alpha-1 and particularly alpha-2 adrenergic receptor radioligand binding sites; neither norepinephrine turnover nor beta adrenergic receptor binding was affected. In brain regions devoid of endogenous epinephrine (cerebellum, frontal cortex and hippocampus), chronic treatment with PNMT inhibitors produced 1) a variable increase in tyrosine hydroxylase activity (cerebellum only) and 2) a reduction in norepinephrine turnover; neither alpha or beta adrenergic receptor binding was altered. A PNMT inhibitor failing to cross the blood-brain barrier, SK&F 29661, and an alpha-1 adrenoceptor antagonist, prazosin, had no effect on brain catecholamine metabolism. High doses of an alpha-2 adrenoceptor antagonist, yohimbine, increased medulla-pons tyrosine hydroxylase activity but also resulted in prominent reductions in norepinephrine content in all brain regions. The results suggest that prolonged reductions in endogenous brain epinephrine formation produce unique effects on brain norepinephrine function; these effects are regionally distinctive and are qualitatively different from the effects seen with chronic alpha-1 or alpha-2 adrenergic receptor blockade. These data are consistent with regulation of brainstem norepinephrine-containing cell bodies by endogenous adrenergic systems, probably via medullary-pontine alpha-2 adrenergic receptors.

Adrenergic alpha-Antagonists↗
PubMed1996

Distribution of tacrine and metabolites in rat brain and plasma after single- and multiple-dose regimens. Evidence for accumulation of tacrine in brain tissue.

Tacrine [1,2,3,4-tetrahydro-9-acridinamine monohydrochloride monohydrate (THA), Cognex] is a potent acetylcholinesterase inhibitor recently approved for treatment of mild-to-moderate Alzheimer's disease. The potential for THA and/or a metabolite of THA to accumulate in brain tissue was investigated by autoradiographic and metabolic profiling techniques in rats given single and multiple doses of [14C]THA. In addition, the brain-to-plasma distribution time course of orally administered 1-hydroxy-THA (1-OH-THA, 24 mg/kg), a primary rat metabolite with anticholinesterase activity, was also examined. Results from a 16 mg/kg single-dose study showed THA to cross the blood-brain barrier readily and concentrate in brain tissue, approximately 5-fold compared with plasma. The metabolite 1-OH-THA was found in much lower amounts relative to THA and when given separately at a similar dose the levels in brain tissue were comparable with plasma concentrations. After multiple-dose administration, THA concentrations in brain tissue were approximately 3-fold higher than those achieved after a single oral dose. However, concentration of 1-OH-THA metabolite increased only 50%. These data suggest a marked difference between the ability of THA and 1-OH-THA to accumulate in brain tissue and may reflect differences in lipophilicity as estimated by calculated log p values. The relevance of THA accumulation in brain tissue to delays observed in THA clinical management of Alzheimer's disease remains to be established.

Animals↗
PubMed1997

Mercury vapor inhalation inhibits binding of GTP to tubulin in rat brain: similarity to a molecular lesion in Alzheimer diseased brain.

Hg2+ interacts with brain tubulin and disassembles microtubules that maintain neurite structure. Since it is well known that Hg vapor (Hg0) is continuously released from "silver" amalgam tooth fillings and is absorbed into brain, rats were exposed to Hg0 4h/day for 0, 2, 7, 14 and 28 d at 250 or 300 micrograms Hg/m3 air, concentrations present in mouth air of some humans with many amalgam fillings. Average rat brain Hg concentrations increased significantly (11-47 fold) with duration of Hg0 exposure. By 14 d Hg0 exposure, photoaffinity labelling on the beta-subunit of the tubulin dimer with [alpha 32P] 8N3 GTP in brain homogenates was decreased 41-74%, upon analysis of SDS-PAGE autoradiograms. The identical neurochemical lesion of similar or greater magnitude is evident in Alzheimer brain homogenates from approximately 80% of patients, when compared to human age-matched neurological controls. Total tubulin protein levels remained relatively unchanged between Hg0 exposed rat brains and controls, and between Alzheimer brains and controls. Since the rate of tubulin polymerization is dependent upon binding of GTP to tubulin dimers, we conclude that chronic inhalation of low-level Hg0 can inhibit polymerization of brain tubulin essential for formation of microtubules.

Administration, Inhalation↗
PubMed1994

Immunocytochemical localization of immunoglobulins in the rat brain: relationship to the blood-brain barrier.

The central nervous system has been traditionally regarded as an immunologically privileged area. This feature has been in part attributed to the blood-brain barrier, which provides a restrictive interface to circulating immunoglobulins (IgG). Recent kinetic studies suggest that the barrier to immune proteins is not absolute, but rather may be regulated by a specific transfer mechanism. In this study, we confirm the presence of IgG in the central nervous system by immunocytochemistry and demonstrate a close anatomical relationship between the distribution of this protein and the blood-brain barrier. IgG was immunolocalized in the normal rat brain by using monoclonal and polyclonal antibodies to IgG and its subclasses. On the basis of an initial evaluation, the most appropriate antibodies and dilutions were selected for subsequent analyses. In the first study, IgG and albumin were immunolocalized in adjacent sections. In the second study, horseradish peroxidase (HRP) was given intravenously prior to sacrifice, in order to examine artifacts related to perfusion fixation. The distribution of HRP and IgG was then examined in adjacent sections. In the third study, IgG was immunolocalized in sections of brain after mild traumatic head injury. A monoclonal antibody to IgG2a and a polyclonal antibody to IgG were selected on the basis of specificity and consistent, mutual localization. Distinct, patchy, perivascular staining, infrequently associated with labeled neurons, was noted throughout the brain. Electron microscopy confirmed the perivascular localization; IgG was localized along the basal lamina of microvasculature and within the adjacent parenchyma. Albumin and HRP did not exhibit a similar pattern of perivascular immunostaining. After head injury, prominent immunostaining for IgG was observed in the injured hemisphere. In summary, these data indicate that the normal rat brain contains IgG, which dramatically increases after head injury. The distinct perivascular distribution in the normal brain suggests local microvascular permeability. This permeability is selective for IgG, since albumin does not share a similar perivascular localization. The neuronal staining which is closely associated with perivascular label may reflect one intracellular route for extravasated IgG.

Albumins↗
PubMed2003

Antioxidant compounds EGB-761 and BN-52021 attenuate brain edema formation and hemeoxygenase expression following hyperthermic brain injury in the rat.

Role of carbon monoxide (CO) in hyperthermic brain injury induced brain pathology was examined in a rat model using immunohistochemistry of the hemeoxygenase-2 (HO-2) enzyme. Exposure of rats to 4 h heat stress at 38 degrees C resulted in profound hyperthermia, breakdown of the blood-brain barrier (BBB), brain edema formation, cell damage and expression of HO-2 in several brain regions. Pretreatment with potent antioxidant compounds EGB-761 and BN-52021 markedly reduced the HO-2 expression, BBB breakdown, brain edema formation and cell damage without attenuating the hyperthermic response. This effect was most marked in animals treated with EGB-761. These observations suggest that upregulation of HO-2 representing generation of CO plays important roles in hyperthermic brain injury, and oxidative stress seems to be one of the most important signals in inducing HO-2 expression in hyperthermia, not reported earlier.

Animals↗
PubMed1997

Role of neurochemicals in brain edema and cell changes following hyperthermic brain injury in the rat.

The involvement of three potent neurochemical mediators of the edema formation such as serotonin, prostaglandins and opioids in the pathophysiology of hyperthermic brain injury was examined in a rat model using a pharmacological approach. Hyperthermic brain injury was induced in conscious young rats by exposing them to heat stress at 38 degrees C for 4 h. In these rats the blood-brain barrier (BBB) permeability, brain edema, cerebral blood flow (CBF), heat shock protein 72 kD (HSP) response and cell changes were examined. Pretreatment with ketanserin (a serotonin-2 receptor antagonist), indomethacin (prostaglandin synthesis inhibitor) and naloxone (opioid receptor antagonist) in separate groups of rats reduced hyperthermia and HSP response following heat stress and significantly attenuated changes in the BBB permeability, brain edema, CBF and cell reaction. These results suggest that the pathophysiology of hyperthermic brain injury is a complex mechanisms and several neurochemicals are involved in the brain pathology caused by heat stress.

Animals↗