ro13-9904 and Brain-Edema

Glutamate (Glu) plays a key role in excitotoxicity-related injury in cerebral ischemia. In the brain, Glu homeostasis depends on Glu transporters, including the excitatory amino acid transporters and the cysteine/Glu antiporter (xc-). We hypothesized that drugs acting on Glu transporters, such as ceftriaxone (CEF, 200 mg/kg, i.p.) and N-acetylcysteine (NAC, 150 mg/kg, i.p.), administered repeatedly for 5 days before focal cerebral ischemia in rats and induced by a 90-min middle cerebral artery occlusion (MCAO), may induce brain tolerance to ischemia. We compared the effects of these drugs on brain infarct volume, neurological deficits and the mRNA and protein expression of the Glu transporter-1 (GLT-1) and xc- with the effects of ischemic preconditioning and chemical preconditioning using 3-nitropropionic acid. Administration of CEF and NAC significantly reduced infarct size and neurological deficits caused by a 90-min MCAO. These beneficial effects were accompanied by changes in GLT-1 expression caused by a 90-min MCAO at both the mRNA and protein levels in the frontal cortex, hippocampus, and dorsal striatum. Thus, the results of this study suggest that the regulation of GLT-1 and xc- plays a role in the development of cerebral tolerance to ischemia and that this regulation may be a novel approach in the therapy of brain ischemia.

Topics: Acetylcysteine; Analysis of Variance; Animals; Brain; Brain Edema; Brain Infarction; Ceftriaxone; Disease Models, Animal; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay; Excitatory Amino Acid Transporter 2; Gene Expression Regulation; Infarction, Middle Cerebral Artery; Male; Nervous System Diseases; Neuroprotective Agents; Rats; Rats, Wistar; RNA, Messenger

Topics: Adult; Anti-Bacterial Agents; Brain Edema; Ceftriaxone; Humans; Magnetic Resonance Imaging; Male; Meningitis, Pneumococcal; Otitis Media; Pneumococcal Infections

Sphingomonas paucimobilis is an aerobic gram-negative bacillus. The bacteria can cause infections, which can be devastating and, therefore, the patients need adequate and early antibiotic cover. We are presenting an interesting case of meningitis secondary to an unusual S. paucimobilis infection. This is the second case to our knowledge in the literature on meningitis due to S. paucimobilis. The 31-year-old previously healthy man presented with 2 months' history of weight loss and loss of appetite. He had fever and headache for 3 weeks. He was also speaking irrelevantly for 3 weeks. He had change of behaviour for 1 day. The patient was a farmer and worked in the soil. On examination, he was not responding to questions and was not obeying commands. Computed tomography (CT) brain with contrast revealed meningeal enhancement and cerebral oedema. Lumbar puncture was performed. Cerebrospinal fluid (CSF) opening pressure was more than 50 cm H2O. CSF analysis showed meningitis picture with raised white cell count of 210/μL (predominantly neutrophils), glucose 3.1 mmol/L, and raised protein 2.47 g/L. He was given intravenous ceftriaxone. The following day, his condition deteriorated. CSF culture grew S. paucimobilis sensitive to ceftriaxone. S. paucimobilis causes severe meningitis. This can lead to hydrocephalus, which results in a need for extraventricular drainage. A good occupational history is important with regard to finding the aetiology of serious meningitis (including rare bacteria) even before the culture result is known. Appropriate treatment can be given early and adequately to prevent mortality.

Topics: Adult; Agricultural Workers' Diseases; Anti-Bacterial Agents; Brain Edema; Ceftriaxone; Cerebrospinal Fluid; Emergencies; Fatal Outcome; Gram-Negative Bacterial Infections; Humans; Hydrocephalus; Male; Meningitis, Bacterial; Sphingomonas; Tomography, X-Ray Computed

Traumatic brain injury (TBI) is a leading cause of mortality and disability in children and young adults worldwide. Neurologic impairment is caused by both immediate brain tissue disruption and post-injury cellular and molecular events that worsen the primary neurologic insult. The β-lactam antibiotic ceftriaxone (CTX) has been reported to induce neuroprotection in animal models of diverse neurologic diseases via up-regulation of GLT-1. However, no studies have addressed the neuroprotective role of CTX in the setting of TBI, and whether the mechanism is involved in the modulation of neuronal autophagy remains totally unclear. The present study was designed to determine the hypothesis that administration of CTX could significantly enhance functional recovery in a rat model of TBI and whether CTX treatment could up-regulate GLT-1 expression and suppress post-TBI neuronal autophagy. The results demonstrated that daily treatment with CTX attenuated TBI-induced brain edema and cognitive function deficits in rats. GLT-1 is down-regulated following TBI and this phenomenon can be reversed by treatment of CTX. In addition, we also found that CTX significantly reduced autophagy marker protein, LC3 II, in hippocampus compared to the TBI group. These results suggest that CTX might provide a new therapeutic strategy for TBI and this protection might be associated with up-regulation of GLT-1 and suppression of neuronal autophagy.

Topics: Animals; Autophagy; Brain Edema; Brain Injuries; Ceftriaxone; Cognition Disorders; Disease Models, Animal; Excitatory Amino Acid Transporter 2; Hippocampus; Male; Maze Learning; Microtubule-Associated Proteins; Neuroprotective Agents; Random Allocation; Rats, Sprague-Dawley; Recovery of Function; Up-Regulation

Evidence has demonstrated that matrix metalloproteinases (MMPs) contribute to the pathophysiology of bacterial meningitis; therefore, MMP inhibitors may be a neuroprotective treatment for brain injury caused by meningitis because of their antiinflammatory effects. The objective of this study was to evaluate the effect of the MMP inhibitor GM6001 in a rat model of S. pneumoniae meningitis. For these experiments, 7-day-old Sprague-Dawley rats were randomly divided into an uninfected group, meningitis group, antibiotic group and GM6001+antibiotic group. Uninfected animals were sham infected with sterile saline. Rats in the other three groups were inoculated with S. pneumoniae and left untreated, treated with ceftriaxone, or treated with ceftriaxone combined with GM6001. Rats in the meningitis group were severely ill, and MMP-9 was significantly up-regulated. The change in brain water content was consistent with the MMP-9 level. A significant loss of neurons and impaired learning function were observed in the meningitis group. Treatment with the antibiotic and GM6001 significantly down-regulated the level of MMP-9, decreased the brain water content, attenuated neuronal injury and improved learning. Conclusions: GM6001 protected the brain from damage caused by S. pneumoniae, and this effect may occur via downregulating MMP-9 and decreasing brain water content.

Topics: Analysis of Variance; Animals; Animals, Newborn; Anti-Bacterial Agents; Brain Edema; Ceftriaxone; Dipeptides; Disease Models, Animal; Gelatinases; Gene Expression Regulation; Matrix Metalloproteinase 1; Matrix Metalloproteinase 9; Maze Learning; Meningitis, Pneumococcal; Rats; Rats, Sprague-Dawley; Spatial Learning; Spatial Memory

The beta-lactam antibiotic, ceftriaxone (CTX), has been reported to induce neuroprotection in animal models of diverse neurologic diseases. Currently, no data have explored the potential for CTX to provide neuroprotection in the animal models of traumatic brain injury (TBI). The aim of this study was to investigate the neuroprotective effect by CTX on TBI and to determine the underlying mechanisms.. Rats were immediately subjected to a lateral cortical impact injury caused by a free-falling object and divided randomly into three groups: sham-operated, trauma, and trauma + CTX treatment group. The CTX treatment group was given CTX (200 mg/kg of body weight, intravenously) immediately after injury. The cognitive function was assessed by Y-maze testing and cerebral edema was evaluated. Inflammatory cytokines expression was measured using enzyme-linked immunosorbent assay array. The expression of glutamate transporter-1 protein was identified by Western blot analysis.. This study shows that the CTX causes attenuation of TBI-induced cerebral edema and cognitive function deficits. CTX treatment significantly reduced levels of the proinflammatory cytokines interleukin-1[beta], interferon-[gamma], and tumor necrosis factor-[alpha] and up-regulated glutamate transporter-1 expression after TBI.. Our results provide in vivo evidence that CTX could exert neuroprotective effect against TBI by improving cognitive function and alleviating brain edema via reducing excitotoxicity and inflammation after TBI.

Topics: Analysis of Variance; Animals; beta-Lactams; Biopsy, Needle; Blotting, Western; Brain Edema; Brain Injuries; Ceftriaxone; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Enzyme-Linked Immunosorbent Assay; Excitatory Amino Acid Transporter 2; Immunohistochemistry; Neuroprotective Agents; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Survival Rate; Treatment Outcome; Up-Regulation

Topics: Acyclovir; Aged; Amphotericin B; Aneurysm; Aneurysm, Infected; Anti-Infective Agents; Brain Edema; Carotid Artery Diseases; Carotid Artery, Internal; Ceftriaxone; Dexamethasone; Embolization, Therapeutic; Equipment Contamination; Female; Humans; Imaging, Three-Dimensional; Infarction, Middle Cerebral Artery; Magnetic Resonance Imaging; Meningoencephalitis; Prostheses and Implants; Prosthesis-Related Infections; Tomography, X-Ray Computed

Patients with End-stage Renal Disease being immunocompromised; are prone to a variety of infections, sometimes, rare ones, more than the general population. This fact should alert the physicians to be more vigilant and have a broader scope when considering the etiology of infections in such patients. We report the case of a 65-year-old man who had a very stormy hospital stay secondary to cerebral nocardiosis with multiple brain abscesses, prolonged unconsciousness and neurological deficits. However, the patient was treated successfully, surgically and chemotherapeutically. He was discharged home in a good condition.

Topics: Aged; Amikacin; Brain Abscess; Brain Diseases; Brain Edema; Ceftriaxone; Humans; Kidney Failure, Chronic; Male; Nocardia Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Unconsciousness; Vancomycin

Multiple brain abscesses are serious neurological problems with high mortality and disabling morbidity. The frequency is rising as a result of AIDS and the increasing number of immunocompromised patients.. A 59-year-old woman developed signs and symptoms of diffuse brain dysfunction including fever and neck stiffness. A brain CT scan demonstrated nine contrast-enhancing ring-shaped lesions. Analysis of the cerebrospinal fluid using PCR-technique revealed DNA of Fusobacterium nucleatum. Conservative treatment with antibiotics was successful. The patient recovered with only mild cognitive deficits.. The experience of our patient and the review of the literature indicate that multiple brain abscesses due to Fusobacterium nucleatum are rare. The most probable source is oral infection.. Multiple brain abscesses may be caused by Fusobacterium nucleatum. Cerebrospinal fluid analysis using PCR technique is helpful with diagnosis. Conservative management can be successful.

Topics: Anti-Bacterial Agents; Brain Abscess; Brain Edema; Ceftriaxone; Cytidine Diphosphate; Dexamethasone; Drug Therapy, Combination; Female; Fusobacterium Infections; Fusobacterium nucleatum; Glucocorticoids; Humans; Metronidazole; Middle Aged; Tomography, X-Ray Computed

Typical features of pneumococcal meningitis have been demonstrated in rats inoculated with Streptococcus pneumoniae. HU-211, a novel noncompetitive N-methyl-D-aspartate antagonist recently demonstrated to inhibit tumor necrosis factor-alpha production under various conditions, improves recovery in some experimental models of brain injury. The present study tested the efficacy of HU-211 in combination with antimicrobial therapy in reducing brain damage in experimental pneumococcal meningitis. S. pneumoniae-infected rats were treated with saline alone, ceftriaxone alone, or with combination of ceftriaxone and HU-211 18 h after inoculation of the bacteria. Brain edema and blood-brain barrier impairment 48 h after infection were significantly (P<.05) reduced suggest that HU-211 when given concomitantly with antibiotics attenuates brain damage in the rat model of pneumococcal meningitis.

Topics: Animals; Blood-Brain Barrier; Brain Edema; Ceftriaxone; Disease Models, Animal; Dronabinol; Drug Therapy, Combination; Male; Meningitis, Pneumococcal; Neuroprotective Agents; Rats; Tumor Necrosis Factor-alpha

Topics: Anticonvulsants; Brain; Brain Edema; Ceftriaxone; Cephalosporins; Child, Preschool; Diarrhea; Dysentery, Bacillary; Feces; Female; Humans; Phenytoin; Seizures; Shigella flexneri; Tomography, X-Ray Computed

A model of experimental lapin meningitis was used to assess the effect of meningeal inflammation caused by Haemophilus influenzae type b on development of brain edema, increase in intracranial pressure, and production of brain lactate. Four treatments were assessed: dexamethasone alone, dexamethasone plus ceftriaxone, ceftriaxone alone, and no treatment. The brain water content in untreated rabbits with meningitis was 419 +/- 10 g of H2O/100g of dry weight after 29 hr of infection (vs. 405 +/- 14 in uninfected rabbits; P less than .05). In rabbits treated with dexamethasone, dexamethasone plus ceftriaxone, or ceftriaxone alone, these values were 404 +/- 12, 406 +/- 12, and 411 +/- 14 g, respectively (P greater than .05). The cerebrospinal fluid (CSF) pressure and lactate levels were significantly increased in all animals during the 24 hr of meningeal inflammation (P less than .005), and these levels were comparably reduced after 9 hr of treatment. Although the values for brain water content, CSF pressure, and lactate concentrations in infected animals treated with ceftriaxone plus dexamethasone were not significantly different from those in animals treated with ceftriaxone alone, the values were consistently lower in the former group.

Topics: Animals; Brain Edema; Ceftriaxone; Cerebrospinal Fluid; Dexamethasone; Drug Therapy, Combination; Haemophilus influenzae; Intracranial Pressure; Lactates; Lactic Acid; Leukocyte Count; Male; Meningitis, Haemophilus; Rabbits

Topics: Adolescent; Adult; Anti-Bacterial Agents; Brain Edema; Cefotaxime; Ceftriaxone; Cephalosporins; Child; Child, Preschool; Chloramphenicol; Humans; Infant; Kinetics; Meningitis; Penicillins; Shock