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Biomedical subjects

D H Smith

Publications and source records attributed to D H Smith.

At least 55 records · Page 3Linked to original sources
PubMed1999

Diffuse axonal pathology detected with magnetization transfer imaging following brain injury in the pig.

This study was designed to evaluate with magnetization transfer imaging (MTI) and conventional magnetic resonance (MR) imaging the manifestation of diffuse axonal injury (DAI) in an animal model of injury via nonimpact coronal plane rotational acceleration. A second objective was to investigate the diagnostic use of quantitative MTR imaging based on statistical parameters in a single subject, as opposed to grouped analysis. Seven mini-swine were subjected to brain trauma known to produce isolated DAI and to MR imaging at two time points. Following sacrifice, the brains were harvested for histopathologic examination. Magnetization transfer ratio (MTR) maps were generated for double-blinded comparison of regions with abnormal MTR values and regions with documented DAI. Positive and negative predictive values for MTR detection of DAI were 67 and 56%, respectively, and in acute studies alone, 89 and 61%. Gains in sensitivity over conventional imaging for detection of DAI were demonstrated.

Animals↗
PubMed1999

Potential decreased morbidity of interstitial brachytherapy for gynecologic malignancies using laparoscopy: A pilot study.

OBJECTIVES: This pilot study was designed to prospectively assess whether the addition of laparoscopy at the time of interstitial brachytherapy is safe, provides verification and/or guidance of needle placement, and results in a reduction of treatment-related morbidity. METHODS: Between 7/93 and 2/97 15 consecutive eligible patients were entered into this study. All patients received external pelvic radiation to a dose range between 45 and 61.20 Gy using 1.8-Gy fractions. In each patient the minimum prescribed dose for the brachytherapy portion was 20 Gy. Minimum cumulative doses to sites of gross disease ranged from 71.8 to 115.3 Gy. A Syed-Neblett afterloading perineal template was used in all the procedures. Laparoscopy using established guidelines was performed during placement of interstitial needles. During template placement, verification of interstitial needles on laparoscopy and any subsequent changes or needle rearrangement were noted. RESULTS: No acute radiation toxicity greater than Grade 2 was noted during the external beam portion of treatment, and no perioperative complications were encountered. These needles were withdrawn under laparoscopic guidance to just below the peritoneal reflection, avoiding proximity to the bowel and improving tumor coverage. Median follow-up time was 26 months. No late radiation morbidity greater than Grade 2 nor any laparoscopic-related complications were noted. To date, one patient has died of disease; six are alive with disease; and eight are alive free of disease with a mean disease-free survival of 17.3 months. CONCLUSION: Laparoscopy at the time of interstitial brachytherapy appears to be safe. No radiation toxicity greater than Grade 2 has developed. No perioperative complications were seen with the addition of laparoscopy. The addition of laparoscopy to the placement of transperineal interstitial implants impacted needle arrangement and/or loading of sources in 50% of patients.

Adult↗
PubMed1999

The economic burden of asthma in US children: estimates from the National Medical Expenditure Survey.

BACKGROUND: Asthma is the leading chronic illness of childhood, is responsible for substantial pediatric morbidity, and has a significant impact on use of health resources. OBJECTIVE: Our purpose was to assess the per capita impact of pediatric asthma on medical care utilization and total expenditures. METHODS: A population-based national probability survey, the National Medical Expenditure Survey, was conducted in 1987 to determine the use and cost of health care services in the United States. We analyzed the responses for all children aged 1 to 17 years with (n = 667) and without (n = 6911) asthma. Children with asthma were identified with use of a population-based screening question. Frequency and cost of medications, ambulatory visits, emergency department care, and hospitalizations for all reasons, including asthma, were assessed. RESULTS: The period prevalence of childhood asthma in 1987 was 8.8% and the treated prevalence (any asthma medications) was 4.0%. Forty-one percent of families with asthmatic children were classified as having no primary insurance. Children with asthma used substantially more services in all categories of care: 3.1 times as many prescriptions, 1.9 times as many ambulatory provider visits, 2. 2 times as many emergency department visits, and 3.5 times as many hospitalizations. Only 10.7% of children with asthma were defined as chronic users of medications. Children with asthma incurred an average of $1129 (SD $5310) per child per year in total health care expenditures compared with $468 (SD $2960) for children without asthma, a 2.8-fold difference. CONCLUSION: Asthma has considerable impact on the use and costs of medical care services among US children. Data from the 1987 National Medical Expenditure Survey provide a useful baseline against which more recent, postguideline data should be compared.

Adolescent↗
PubMed1999

Comparisons of the effects of different long-acting delivery systems on the pharmacokinetics and pharmacodynamics of diltiazem.

The benzothiazepine calcium channel antagonist diltiazem is a short-acting drug. To achieve effective 24-h blood pressure control with once-daily dosing, it relies on various extended drug-delivery systems that have grown in importance as a result of the recent reports relating the use of short-acting calcium channel antagonists to increased cardiovascular morbidity. This study examines the pharmacokinetics and resulting pharmacodynamics of two different delivery systems, each loaded with 240 mg of diltiazem and administered to 40 moderately hypertensive patients in a randomized, double-blind crossover trial. After a 4-week, single-blind placebo lead-in, patients with a clinical diastolic blood pressure of > or =100 mm Hg were randomized to either the single or dual microbead diltiazem delivery system for a 4-week period. At the end of this period, each subject was evaluated with 24-h ambulatory blood pressure monitoring and subjected to 24-h inpatient pharmacokinetic analysis on separate days. This was followed by a similar 4-week period in which each subject was treated with the alternative delivery system. For diltiazem, the area under the curve for plasma concentration versus time and the maximum plasma concentration attained by the single microbead system exceeded the values achieved by the dual bead system by 15% and 25%, respectively. These differences were greatest from the 3rd through the 13th h after dosing. During this period, both systolic and diastolic ambulatory blood pressure was significantly lower when the single microbead system was used. When compared with baseline blood pressure, blood pressure reductions achieved with the single microbead system exceeded reductions achieved with the dual microbead system by at least 2 mm Hg for 10 of the 24 postdose hours. Heart rates were slightly reduced but not significantly different. This improved blood pressure control at higher plasma levels of diltiazem suggests that a more efficient delivery system could provide better blood pressure control for identical doses of diltiazem.

Adult↗
PubMed1999

Is high blood pressure a late manifestation of the hypertension syndrome?

Because hypertension has generally been defined as a disease of elevated systolic and diastolic blood pressure, the goals of treating hypertension have been simply to normalize the blood pressure. It was believed that if normal blood pressure were achieved, patients with hypertension would experience significant reductions in the incidence of associated cardiovascular events. However, studies to assess cardiovascular events in patients with hypertension have repeatedly demonstrated that reducing blood pressure results in very impressive reductions in cerebrovascular disease but in reductions of only about 16% in coronary artery disease, which is far lower than what was statistically predicted from the reductions in blood pressure. Although there are probably several reasons for the poor rate of reductions in the incidence of coronary artery disease, one of the most compelling appears to be the realization that hypertension is not simply a disease of numbers but rather a complex inherited syndrome of cardiovascular risk factors, all of which contribute to the development of heart disease in these patients. Included in the hypertension syndrome are abnormalities of lipid profile and insulin resistance, changes in renal function, endocrine changes, obesity, abnormalities of coagulation factors, and changes in the structure and function of the left ventricle and of vascular smooth muscle in the vasculature. In many patients, high blood pressure is a late manifestation of this disease process and is preceded by some or all of the associated cardiovascular risk factors. This paradigm suggests that therapeutic strategies for hypertension should be interventions that target both the hemodynamic and nonhemodynamic mechanisms of this syndrome to more completely reduce cardiovascular morbidity and mortality in patients with hypertension.

Antihypertensive Agents↗
PubMed1999

Hypertension control: multifactorial contributions.

Treatment of hypertension reduces the risk of several associated deleterious conditions, although it does not lower risk for all cardiovascular diseases. A new theory suggests that high blood pressure is but one piece in the puzzle of a complex syndrome of inherited risk factors called the hypertension syndrome. Several new findings have emerged theorizing that patients may have coronary artery disease before the actual onset of elevated blood pressure. Epidemiologic studies have found that normotensive patients with a family history of hypertension often have a disease process and prognosis similar to that of hypertensives. It seems that some patients may "inherit" abnormalities that make them prone to the development of hypertension, as well as a complex series of cardiovascular disease risk factors. These include elevated lipids, increased left ventricular hypertrophy, arterial stiffening, insulin resistance, renal function abnormalities, and neuroendocrine changes. It is conceivable that the hypertension syndrome may be reversible if the disease process is diagnosed early, which appears to be well before the actual onset of high blood pressure. High blood pressure may be a risk marker for irreversible vascular disease and early detection of the many components of hypertension syndrome may delay or prevent cardiovascular disease from developing in high-risk patients.

Angiotensin Receptor Antagonists↗
PubMed1999

Prolonged activation of NF-kappaB following traumatic brain injury in rats.

Activation of transcription factor, nuclear factor kappa B (NF-kappaB), has been shown to play a key role in inflammatory response, neuronal survival and signaling. We investigated the regional and temporal distribution of activated NF-kappaB in rats at 1 h, 2 h, 24 h, 48 h, 1 week, 2 weeks, 1 month, 2 months, 6 months, and 1 year following brain injury in rats. Early after trauma (1-2 h), activated NF-kappaB was detected in axons, and subsequently found in the cytoplasm and nucleus of neurons by 24 h and lasting up to 1 week. In addition, by 24 h posttrauma, activated NF-kappaB was detected in microglia/macrophages and astrocytes in injured cortex. Surprisingly, this activation persisted for at least 1 year following injury in the cortex, primarily at the margins of progressively enlarging ventricle. Activated NF-kappaB was also detected in endothelial cells, as early as 1 h, and persisted for up to 1 year. These results suggest that a neuronal response to brain trauma includes the activation of NF-kappaB first in the axon with subsequent translocation to the nucleus. Furthermore, these results demonstrate that remarkably prolonged activation of NF-kappaB in glia is found in the same regions undergoing persistent atrophy, suggesting NF-kappaB activation may play a role in long-term inflammatory processes following brain trauma.

Animals↗
PubMed1999

Experimental investigation of cerebral contusion: histopathological and immunohistochemical evaluation of dynamic cortical deformation.

We used a new approach, termed dynamic cortical deformation (DCD), to study the neuronal, vascular, and glial responses that occur in focal cerebral contusions. DCD produces experimental contusion by rapidly deforming the cerebral cortex with a transient, nonablative vacuum pulse of short duration (25 milliseconds) to mimic the circumstances of traumatic injury. A neuropathological evaluation was performed on brain tissue from adult rats sacrificed 3 days following induction of either moderate (4 psi, n = 6) or high (8 psi, n = 6) severity DCD. In all animals, DCD produced focal hemorrhagic lesions at the vacuum site without overt damage to other regions. Examination of histological sections showed localized gross tissue and neuronal loss in the cortex at the injury site, with the volume of cell loss dependent upon the mechanical loading (p < 0.001). Axonal pathology shown with neurofilament immunostaining (SMI-31 and SMI-32) was observed in the subcortical white matter inferior to the injury site and in the ipsilateral internal capsule. No axonal injury was observed in the contralateral hemisphere or in any remote regions. Glial fibrillary acidic protein (GFAP) immunostaining revealed widespread reactive astrocytosis surrounding the necrotic region in the ipsilateral cortex. This analysis confirms that rapid mechanical deformation of the cortex induces focal contusions in the absence of primary damage to remote areas 3 days following injury. Although it is suggested that massive release of neurotoxic substances from a contusion may cause damage throughout the brain, these data emphasize the importance of combined injury mechanisms, e.g. mechanical distortion and excitatory amino acid mediated damage, that underlie the complex pathology patterns observed in traumatic brain injury.

Animals↗
PubMed1999

Evolution of neurofilament subtype accumulation in axons following diffuse brain injury in the pig.

Although accumulation of neurofilament (NF) proteins in axons has been recognized as a prominent feature of brain trauma, the temporal course of the accumulation of specific NF subtypes has not been well established. In the present study, 17 miniature swine were subjected to nonimpact inertial brain injury. At 3 hours (h), 6 h, 24 h, 3 days, 7 days, and 10 days post-trauma, immunohistochemical analysis was performed to determine axonal accumulation of NF-light (NF-L), the rod and sidearm domains and sidearm phosphorylation states of NF-medium (NF-M), and heavy (NF-H). We found that NF-L accumulation was easily identified in damaged axons by 6 h post-trauma, but NF-M and H accumulation was not clearly visualized until 3 days following injury. In addition, the axonal accumulation of NF-M and H appeared to be primarily comprised of the sidearm domains. While the accumulating NF was found to be predominantly dephosphorylated, we also detected accumulation of phosphorylated NF. Finally, we found that developing axonal pathology may proceed either towards axotomy with discrete terminal bulb formation or towards the development of varicose swellings encompassing long portions of axons. These findings suggest that there is a differential temporal course in NF subtype disassembly, dephosphorylation, and accumulation in axons following initial brain trauma and that these processes occur in morphologically distinct phenotypes of maturing axonal pathology.

Animals↗
PubMed1999

Accumulation of amyloid beta and tau and the formation of neurofilament inclusions following diffuse brain injury in the pig.

Brain trauma in humans increases the risk for developing Alzheimer disease (AD) and may induce the acute formation of AD-like plaques containing amyloid beta (A beta). To further explore the potential link between brain trauma and neurodegeneration, we conducted neuropathological studies using a pig model of diffuse brain injury. Brain injury was induced in anesthetized animals via nonimpact head rotational acceleration of 110 degrees over 20 ms in the coronal plane (n = 15 injured, n = 3 noninjured). At 1, 3, 7, and 10 days post-trauma, control and injured animals were euthanized and immunohistochemical analysis was performed on brain sections using antibodies specific for A beta, beta-amyloid precursor protein (betaPP), tau, and neurofilament (NF) proteins. In addition to diffuse axonal pathology, we detected accumulation of A beta and tau that colocalized with immunoreactive betaPP and NF in damaged axons throughout the white matter in all injured animals at 3-10 days post-trauma. In a subset of brain injured animals, diffuse A beta-containing plaque-like profiles were found in both the gray and white matter, and accumulations of tau and NF rich inclusions were observed in neuronal perikarya. These results show that this pig model of diffuse brain injury is characterized by accumulations of proteins that also form pathological aggregates in AD and related neurodegenerative diseases.

Amyloid beta-Peptides↗
PubMed1999

Evaluation of protein A gene polymorphic region DNA sequencing for typing of Staphylococcus aureus strains.

Three hundred and twenty isolates of Staphylococcus aureus were typed by DNA sequence analysis of the X region of the protein A gene (spa). spa typing was compared to both phenotypic and molecular techniques for the ability to differentiate and categorize S. aureus strains into groups that correlate with epidemiological information. Two previously characterized study populations were examined. A collection of 59 isolates (F. C. Tenover, R. Arbeit, G. Archer, J. Biddle, S. Byrne, R. Goering, G. Hancock, G. A. Hébert, B. Hill, R. Hollis, W. R. Jarvis, B. Kreiswirth, W. Eisner, J. Maslow, L. K. McDougal, J. M. Miller, M. Mulligan, and M. A. Pfaller, J. Clin. Microbiol. 32:407-415, 1994) from the Centers for Disease Control and Prevention (CDC) was used to test for the ability to discriminate outbreak from epidemiologically unrelated strains. A separate collection of 261 isolates form a multicenter study (R. B. Roberts, A. de Lencastre, W. Eisner, E. P. Severina, B. Shopsin, B. N. Kreiswirth, and A. Tomasz, J. Infect. Dis. 178:164-171, 1998) of methicillin-resistant S. aureus in New York City (NYC) was used to compare the ability of spa typing to group strains along clonal lines to that of the combination of pulsed-field gel electrophoresis and Southern hybridization. In the 320 isolates studied, spa typing identified 24 distinct repeat types and 33 different strain types. spa typing distinguished 27 of 29 related strains and did not provide a unique fingerprint for 4 unrelated strains from the four outbreaks of the CDC collection. In the NYC collection, spa typing provided a clonal assignment for 185 of 195 strains within the five major groups previously described. spa sequencing appears to be a highly effective rapid typing tool for S. aureus that, despite some expense of specificity, has significant advantages in terms of speed, ease of use, ease of interpretation, and standardization among laboratories.

Amino Acid Sequence↗
PubMed1999

Comparative characterization of rep proteins from the helper-dependent adeno-associated virus type 2 and the autonomous goose parvovirus.

Adeno-associated viruses (AAVs) are nonautonomous human parvoviruses in that they are dependent on helper functions supplied by other viruses or on genotoxic stimuli for conditions permissive for replication. In the absence of helper, AAV type 2 enters latency by integration into a specific site on human chromosome 19. This feature of AAV, in combination with a lack of pathogenicity, makes AAV an attractive candidate vector for human gene therapy. Goose parvovirus (GPV) is both autonomous and pathogenic yet is highly homologous to AAV. To address the molecular bases for the different viral lifestyles, we compare the AAV and GPV nonstructural proteins, Rep78 and Rep1, respectively. We find that Rep78 and Rep1 possess several biochemical activities in common, including (i) high-affinity DNA binding for sequences that constitute the minimal DNA replication origin; (ii) nucleoside triphosphate-dependent DNA helicase activity; and (iii) origin-specific replication of double-stranded linear DNA. These experiments also establish a specific 38-bp DNA sequence as the minimal GPV DNA replication origin. It is noteworthy that although the proposed Rep binding sites of GPV and AAV are highly similar, Rep1 and Rep78 show a high degree of specificity for their respective origins, in both binding and replication assays. One significant difference was observed; with the minimal replication origin in adenovirus-uninfected extracts, Rep78-mediated replication exhibited low processivity, as previously reported. In contrast, Rep1 efficiently replicated full-length template. Overall, our studies indicate that GPV Rep1 and AAV Rep78 support a comparable mode of replication. Thus, a comparison of the two proteins provides a model system with which to determine the contribution of Rep in the regulation of dependence and autonomy at the level of DNA replication.

Animals↗
PubMed1999

Kinetics of antibody response to Haemophilus influenzae type b vaccines. Pennridge Pediatric Associates.

Serum antibodies to the capsular polysaccharide of Haemophilus influenzae type b (Hib) are effective in preventing or ameliorating invasive disease caused by this human pathogen. Polysaccharide and conjugate (saccharide covalently linked to protein carrier) vaccines have been developed which stimulate the production of such antibodies. The polysaccharide-specific antibody concentrations in the sera of vaccine-naïve adults and toddlers on days 1, 3, 7, 14 and 28 following immunisation with one dose of the Hib polysaccharide vaccine (PRP, polyribosylribitol phosphate) or an oligosaccharide-CRM197 conjugate vaccine (HbOC, HibTITER) were determined. Antibody responses occurred within 7 days of immunisation with the maximum response usually occurring 14 days post-immunisation, irrespective of vaccine or subject age. In this small study, a significant transient decline in pre-existing antibodies was observed only in the groups receiving the polysaccharide vaccine and not in the groups receiving HbOC vaccine. Because of the small magnitude of antigen-specific antibody decline and its transient nature, it is unlikely that this observation has clinical significance.

Adult↗
PubMed1999

What are the approaches for evaluating antihypertensive treatment by 24 h ambulatory blood pressure monitoring?

Measurements of trough blood pressure in a clinic setting have been the traditional method of assessing the efficacy of antihypertensive agents. The duration of action of antihypertensive drugs has been assessed by calculation of a trough-to-peak ratio; drugs with a trough-to-peak ratio greater than 50% are typically given once-a-day indications. However, the use of clinical measurements to assess antihypertensive agents can be misleading. Ambulatory blood pressure monitoring is a simple technique that provides accurate and reproducible data on both the efficacy and duration of action of antihypertensive agents. Although several complicated techniques have been used for the analysis of ambulatory blood pressure data, studies have demonstrated that calculation of simple blood pressure means (24 h mean, day-time mean and night-time mean) will provide all the data required to assess the efficacy of a drug. Calculations of systolic and diastolic load also provide useful information, and the index correlates closely with target-organ damage. Assessing the reduction of blood pressure during the last 2-6 h of the dosing interval provides critical information on the duration of action of agents with once-a-day dosing. Trough-to-peak ratio can also be calculated from an ambulatory blood pressure monitor. Furthermore, a simple line graph constructed from hourly means makes available, at a simple glance, a large amount of information about a drug. The reproducibility of ambulatory monitoring, together with the absence of placebo effect and the ability to exclude patients with white-coat hypertension, make the technique an extremely powerful tool for the assessment of antihypertensive agents that clearly provides more data on the efficacy and duration of action of an antihypertensive agent than do traditional clinical measurements.

Antihypertensive Agents↗
PubMed1998

Prevalence and transmission of Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in Ugandan children and adolescents.

We studied the seroprevalence and transmission of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8), among 215 Ugandan children, adolescents and young adults. We measured antibodies to a latent nuclear antigen (LANA) and a lytic cycle protein encoded by open reading frame (orf) 65. Infection with KSHV/HHV8 occurred during early childhood and reached adult levels (approx. 50%) before the age of puberty. In children younger than 12 years of age, antibodies to LANA and the orf65 protein were independently associated with hepatitis B infection (p < 0.005). KSHV/HHV8 infection was not associated with antibodies to hepatitis A virus and hepatitis C virus, nor with the quality of the water supply, household size, previous blood transfusions, number of boy/girl friends or marital status. Antibodies to the orf65 protein, but not LANA, were weakly associated with a history of i.v. injections. Our results show that, in contrast to its sexual mode of transmission among homo/bisexual men and sexually transmitted diseases clinic attendees of Northern Europe and the US, transmission of KSHV in Uganda occurs largely before puberty. Among Ugandan children, KSHV transmission follows a horizontal pattern similar to other herpesviruses, in particular the related gamma herpesvirus, Epstein-Barr virus. Transmission of KSHV may be facilitated by living conditions that also promote infection with hepatitis B virus.

Adolescent↗
PubMed1998

Effects of the NMDA antagonist CP-98,113 on regional cerebral edema and cardiovascular, cognitive, and neurobehavioral function following experimental brain injury in the rat.

The present study examined the effects of CP-98,113, an N-methyl-d-aspartate (NMDA) receptor blocker, on cardiovascular variables, neurobehavioral motor function, spatial memory deficits, and cerebral edema formation following lateral (parasagittal) fluid-percussion (FP) brain injury in the rat. In Study 1, we compared the cardiovascular effects of i.p. administration of CP-98, 113 at 15 min postinjury at doses of 1 mg/kg, 2 mg/kg, 5 mg/kg, or 20 mg/kg (n=8/dose). Animals receiving 1 mg/kg to 5 mg/kg CP-98,113 showed slight but nonsignificant decreases in blood pressure, while those receiving the highest dose (20 mg/kg) showed significant hypotension. Based upon those observations, the 5 mg/kg dose was chosen as the optimal dose for subsequent behavioral studies. In Study 2, 15 min following lateral FP brain injury of moderate severity (2.5 atm), animals randomly received either CP-98,113 (5 mg/kg, i.p., n=23) followed by a 24-h subcutaneous infusion (1.5 mg kg-1 h-1) by means of a miniature osmotic pump, or identical volume of vehicle (n=24), and were evaluated for neurologic motor function (n=11/drug vs. 11/vehicle), memory function, and cerebral edema (n=12/drug vs. 13/vehicle). CP-98,113 (5 mg/kg) significantly attenuated neurologic motor dysfunction at 24 h (p<0.01) and 2 weeks (p<0.05) postinjury, reduced posttraumatic impairment in spatial memory observed at 48 h postinjury (p<0.001), and significantly reduced focal brain edema in the cortex adjacent to the site of maximal injury at 48 h postinjury (injury penumbra) (p<0.001). These results suggest that blockade of the NMDA receptor may attenuate the deleterious sequelae of traumatic brain injury.

Animals↗
PubMed1998

Riluzole attenuates cortical lesion size, but not hippocampal neuronal loss, following traumatic brain injury in the rat.

The neuroprotective effects of Riluzole, a compound with several mechanisms of action including the inhibition of sodium channel activity and glutamate release, were evaluated in a rat model of parasagittal fluid-percussion (FP) brain injury. Male Sprague-Dawley rats (350-400 g, n = 17) were anesthetized with sodium pentobarbital (60 mg/kg i.p.) and subjected to parasagittal FP brain injury of moderate severity (2.3-2.5 atm). Fifteen min following injury, animals randomly received an i.v. bolus of either Riluzole (8 mg/kg, n = 8) or vehicle (n = 9), followed by subcutaneous injections (identical dose) at 6 hr and 24 hr. Two weeks after injury and drug treatment, animals were sacrificed and a series of brain sections, stained with Hematoxylin and Eosin (H&E) or cresyl violet, were evaluated for quantitative cortical lesion volume and cell counts of hippocampal CA3 neurons, respectively, using a computerized image analysis system. Administration of Riluzole significantly reduced FP-induced tissue loss in the temporal/occipital cortices ipsilateral to the site of impact by 46%, compared to vehicle-treated, brain-injured animals (P = 0.01). In contrast, the selective neuronal loss observed in the CA3 region of the ipsilateral hippocampus was unaffected by Riluzole treatment. The present study demonstrates that Riluzole can attenuate cortical lesion size following brain trauma. These neuroprotective effects may be related to the synergy of the different mechanisms of action of Riluzole.

Animals↗