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Biomedical subjects

J M Parent

Publications and source records attributed to J M Parent.

At least 19 recordsLinked to original sources
PubMed2000

X-irradiation causes a prolonged reduction in cell proliferation in the dentate gyrus of adult rats.

The effects of X-irradiation on proliferating cells in the dentate subgranular zone were assessed in young adult Fisher 344 rats exposed to a range of X-ray doses and followed for up to 120 days. Apoptosis was quantified using morphology and end-labeling immunohistochemistry, and cell proliferation was detected using antibodies against the thymidine analog BrdU and the cyclin-dependent kinase p34(cdc2). Radiation-induced apoptosis occurred rapidly, with maximum morphological and end-labeling changes observed 3-6h after irradiation. Twenty-four hours after irradiation cell proliferation was significantly reduced relative to sham-irradiated controls. The number of apoptotic nuclei increased rapidly with radiation dose, reaching a plateau at about 3Gy. The maximum number of apoptotic nuclei was substantially higher than the number of proliferating cells, suggesting that non-proliferating as well as proliferating cells in the subgranular zone were sensitive to irradiation. Subgranular zone cell proliferation was significantly reduced relative to age-matched controls 120 days after doses of 5Gy or higher. These findings suggest that neural precursor cells of the dentate gyrus are very sensitive to irradiation and are not capable of repopulating the subgranular zone at least up to 120 days after irradiation. This may help explain, in part, how ionizing irradiation induces cognitive impairments in animals and humans.

Animals↗
PubMed2000

Effect of clomipramine on monoamine metabolites in the cerebrospinal fluid of behaviorally normal dogs.

The tricyclic antidepressant, clomipramine, is an effective treatment for canine compulsive disorder (canine CD). This disorder is a clinical syndrome of abnormal conflict behaviors and its pathophysiology is unknown. However, because clomipramine is an effective treatment, information about the drug's neurochemical effect could enhance the understanding of canine CD. The following experiment used 6 behaviorally normal dogs to assess the effect of clomipramine (3 mg/kg, q24h, PO) on the central turnover of 3 monoamines (serotonin, dopamine, and norepinephrine) as measured by the concentrations of their respective metabolites in cerebrospinal fluid (CSF). In a randomized, placebo-controlled, AB-BA crossover experiment, cisternal CSF was taken after 1, 2, 4, and 6 wk on each treatment. No effect of clomipramine was detected. This contrasts with human studies that have suggested that clomipramine affects the concentrations of monoamine metabolites in lumbar CSF. However, those papers do not address methodological assumptions, such as (i) metabolites in CSF originate only from the brain, and (ii) concentrations of metabolites in cisternal/lumbar CSF reflect the concentrations in local areas of the brain. Notwithstanding the small sample size, our results suggest that more localized sampling techniques (e.g. microdialysis) are needed when examining the effect of drugs on central monoamine metabolites. Clomipramine's efficacy for canine CD indicates the need for neurobiological research and, to our knowledge, our study is the first of its kind in dogs. The resulting data are preliminary but they can inform optimal neurobiological studies of canine CD.

Administration, Oral↗
PubMed1999

Clinical findings, treatment, and outcome of dogs with status epilepticus or cluster seizures: 156 cases (1990-1995).

OBJECTIVE: To report clinical findings, treatments, and outcomes of dogs admitted to the hospital for status epilepticus or cluster seizures and evaluate factors associated with outcome. DESIGN: Retrospective study. ANIMALS: 156 dogs admitted for status epilepticus or cluster seizures. PROCEDURE: Medical records were reviewed for seizure and medication history, diagnostic test results, types of treatment, hospitalization costs, and outcome of hospital visits. RESULTS: Dogs were admitted for seizures on 194 occasions. Of 194 admissions, 128 (66%), 2 (1%), 32 (16.5%), 2 (1%), and 30 (15.5%) were of dogs with a history of clusters of generalized seizures, clusters of partial complex seizures, convulsive status epilepticus, partial status epilepticus, and > 1 type of seizure, respectively. Underlying causes of seizures were primary epilepsy (26.8%; 52/194), secondary epilepsy (35.1%; 68), reactive epileptic seizures (6.7%; 13), primary or secondary epilepsy with low serum antiepileptic drug concentrations (5.7%; 11), and undetermined (25.8%; 50). One hundred and eighty-six hospital visits resulted in admission to the intensive care unit (ICU). Treatments with continuous i.v. infusions of diazepam or phenobarbital were initiated during 66.8% (124/186) and 18.7% (35) of ICU hospital stays for 22.3 +/- 16.1 hours (mean +/- SD) and 21.9 +/- 15.4 hours, respectively. Of 194 admissions, 74.7% (145) resulted in discharge from the hospital, 2.1% (4) in death, and 23.2% (45) in euthanasia. A poor outcome (death or euthanasia) was significantly associated with granulomatous meningoencephalitis, loss of seizure control after 6 hours of hospitalization, and the development of partial status epilepticus. CONCLUSIONS AND CLINICAL RELEVANCE: Granulomatous meningoencephalitis, loss of seizure control after 6 hours of hospitalization, or the development of partial status epilepticus may indicate a poor prognosis for dogs with seizures.

Animals↗
PubMed1999

Inhibition of dentate granule cell neurogenesis with brain irradiation does not prevent seizure-induced mossy fiber synaptic reorganization in the rat.

Aberrant reorganization of dentate granule cell axons, the mossy fibers, occurs in human temporal lobe epilepsy and rodent epilepsy models. Whether this plasticity results from the remodeling of preexisting mossy fibers or instead reflects an abnormality of developing dentate granule cells is unknown. Because these neurons continue to be generated in the adult rodent and their production increases after seizures, mossy fibers that arise from either developing or mature granule cells are potential substrates for this network plasticity. Therefore, to determine whether seizure-induced, mossy fiber synaptic reorganization arises from either developing or mature granule cell populations, we used low-dose, whole-brain x-irradiation to eliminate proliferating dentate granule cell progenitors in adult rats. A single dose of 5 Gy irradiation blocked cell proliferation and eliminated putative progenitor cells in the dentate subgranular proliferative zone. Irradiation 1 d before pilocarpine-induced status epilepticus significantly attenuated dentate granule cell neurogenesis after seizures. Two irradiations, 1 d before and 4 d after status epilepticus, essentially abolished dentate granule cell neurogenesis but failed to prevent mossy fiber reorganization in the dentate molecular layer. These results indicate that dentate granule cell neurogenesis in the mature hippocampal formation is vulnerable to the effects of low-dose ionizing irradiation. Furthermore, the development of aberrant mossy fiber remodeling in the absence of neurogenesis suggests that mature dentate granule cells contribute substantially to seizure-induced network reorganization.

Animals↗
PubMed1998

Efficacy of clomipramine in the treatment of canine compulsive disorder.

OBJECTIVE: To assess the efficacy of clomipramine for treatment of canine compulsive disorder (CCD). DESIGN: Randomized, placebo-controlled, double-blind, balanced AB-BA crossover clinical study. ANIMALS: 51 dogs with CCD. PROCEDURES: Dogs were given clomipramine (3 mg/kg [1.3 mg/lb] of body weight, PO, q 12 h) for 4 weeks and placebo for 4 weeks. At the end of each treatment each owner rated the severity of their dog's behavior, using 2 validated rating scales. Statistical analysis was made by ordinal regression. Compliance, adverse effects, and the effectiveness of masking were also assessed. Each dog's behavior was reevaluated 1 to 2 years after completing the study. RESULTS: Behaviors included spinning (n = 17) and self-mutilation by licking (acral lick dermatitis, 12). Both rating scales demonstrated a treatment effect. Compliance was satisfactory, and masking was effective. Sedation and reduced appetite were reported more commonly when dogs were given clomipramine than when they were given placebo. Forty-five dogs available for follow-up evaluation still had their behaviors; 6 dogs were lost to follow-up evaluation. CLINICAL IMPLICATIONS: Results suggest that clomipramine was effective in dogs with CCD and was not associated with serious adverse effects. However, treatment for 4 weeks was not curative. Behavior modification is likely to be necessary to manage CCD.

Animals↗
PubMed1998

Increased dentate granule cell neurogenesis following amygdala kindling in the adult rat.

Structural neuronal network plasticity is associated with epileptogenesis during limbic kindling, but the full extent of network changes is not well understood. We investigated whether dentate granule cell (DGC) neurogenesis, which continues into adulthood in the rodent, is altered in the amygdala kindling model of epileptogenesis. Adult rats were stimulated to either 4-6, 9-10 or 19-20 class 4/5 (generalized) kindled seizures. 5-Bromo-2'-deoxyuridine labeling showed that cell proliferation increased in the dentate gyrus only in animals that experienced nine or more class 4/5 kindled seizures. Immunocytochemistry for neuronal markers revealed that many of the newly generated cells differentiated into DGCs in the inner aspect of the DGC layer. The lack of increased DGC neurogenesis after fewer kindled seizures or at early timepoints following kindling suggests that this process is not involved in kindling development. Instead, newly generated DGCs may be important for maintenance of the kindled state or the increased susceptibility to spontaneous recurrent seizures.

Amygdala↗
PubMed1997

Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus.

The dentate granule cell layer of the rodent hippocampal formation has the distinctive property of ongoing neurogenesis that continues throughout adult life. In both human temporal lobe epilepsy and rodent models of limbic epilepsy, this same neuronal population undergoes extensive remodeling, including reorganization of mossy fibers, dispersion of the granule cell layer, and the appearance of granule cells in ectopic locations within the dentate gyrus. The mechanistic basis of these abnormalities, as well as their potential relationship to dentate granule cell neurogenesis, is unknown. We used a systemic chemoconvulsant model of temporal lobe epilepsy and bromodeoxyuridine (BrdU) labeling to investigate the effects of prolonged seizures on dentate granule cell neurogenesis in adult rats, and to examine the contribution of newly differentiated dentate granule cells to the network changes seen in this model. Pilocarpine-induced status epilepticus caused a dramatic and prolonged increase in cell proliferation in the dentate subgranular proliferative zone (SGZ), an area known to contain neuronal precursor cells. Colocalization of BrdU-immunolabeled cells with the neuron-specific markers turned on after division, 64 kDa, class III beta-tubulin, or microtubule-associated protein-2 showed that the vast majority of these mitotically active cells differentiated into neurons in the granule cell layer. Newly generated dentate granule cells also appeared in ectopic locations in the hilus and inner molecular layer of the dentate gyrus. Furthermore, developing granule cells projected axons aberrantly to both the CA3 pyramidal cell region and the dentate inner molecular layer. Induction of hippocampal seizure activity by perforant path stimulation resulted in an increase in SGZ mitotic activity similar to that seen with pilocarpine administration. These observations indicate that prolonged seizure discharges stimulate dentate granule cell neurogenesis, and that hippocampal network plasticity associated with epileptogenesis may arise from aberrant connections formed by newly born dentate granule cells.

Animals↗
PubMed1997

Diagnostic evaluation of cats with seizure disorders: 30 cases (1991-1993).

OBJECTIVE: To investigate causes of seizure disorders in cats. DESIGN: Case series. ANIMALS: 30 cats referred to the Ontario Veterinary College for recurrent seizures. PROCEDURES: Signalment and seizure pattern were evaluated. Diagnostic procedures included physical, neurologic, and fundic examinations; CBC; serum biochemical analyses, including determination of pre- and postprandial bile acid concentrations; urinalysis; serologic assays for FeLV and feline immunodeficiency virus, feline infectious peritonitis, and Toxoplasma gondii, magnetic resonance imaging of the brain; CSF analysis; and neuropathologic examination of euthanatized cats and of surgical biopsy specimens. RESULTS: All cats were found to have structural brain diseases; nonsuppurative meningoencephalitis of unknown cause was found in 14 cats, feline ischemic encephalopathy in 6, meningioma in 2, polycythemia vera with secondary brain lesions in 2, posttraumatic epilepsy in 1, and cerebral abscess in 1. A definitive diagnosis could not be reached in 4 cats. CLINICAL IMPLICATIONS: The most common cause of seizures in cats is structural brain disease. Structural brain lesions often can be detected on the basis of seizure pattern and results of neurologic examination. Cerebrospinal fluid analysis and brain imaging are essential to determine the cause of these lesions. Causes of seizures found in the cats of this study differ from those reported to be the most common. Nonsuppurative meningoencephalitis of unknown origin appears to be a frequent cause of neurologic disorders in cats, including seizure disorders. Feline ischemic encephalopathy appears to exist in a milder form than the classic disease and may be a common cause of seizures in cats.

Animals↗
PubMed1997

Clinical management and outcome of cats with seizure disorders: 30 cases (1991-1993).

OBJECTIVE: To determine outcome of clinical management of cats with seizure disorders. DESIGN: Case series. ANIMALS: 30 cats referred to the Ontario Veterinary College for recurrent seizures. PROCEDURES: Treatment was dictated by the cat's seizure frequency and by the underlying cause. Cats that were having cluster seizures or status epilepticus at the time of admission were treated orally with phenobarbital and with constant IV administration of diazepam. The other cats were treated with long-term oral administration of phenobarbital if the frequency of their seizures justified it. Follow-up included evaluation of seizure frequency, serum antiepileptic drug concentrations, and hematologic and serum biochemical values. Outcome was documented on the basis of survival and seizure frequency at the end of the followup period, which ranged from 3 to 21 months. RESULTS: 6 cats were euthanatized without any therapeutic attempts at the owners' request. Twenty of the remaining 24 cats were alive at the time of final follow-up. Seventeen had a good outcome; 11 were not having any more seizures and 6 were having a low frequency of seizures. For 3 other cats, seizures were not well controlled. Four cats had been euthanatized (2 because of intractable seizures, 1 because of postcraniotomy complications, and 1 because the owners did not want to pursue treatment). CLINICAL IMPLICATIONS: Results suggest that severity of seizure disorder in cats is not a good predictor of outcome and that aggressive treatment is often rewarding, even in the most severe cases.

Administration, Oral↗
PubMed1997

Mossy fiber reorganization in the epileptic hippocampus.

Reorganization of dentate granule cell axons (mossy fibers) is a prominent aspect of the pathological changes observed in human temporal lobe epilepsy. Although recent work has begun to address the significance of mossy fiber reorganization, the specific and overall functional consequences of these network changes remain poorly understood. New studies are beginning to provide insight into molecular mechanisms underlying this process. Advances in our understanding of the causes and effects of mossy fiber reorganization are likely to provide insight into the pathophysiology of temporal lobe epilepsy, as well as the larger issue of network remodeling following nervous system injury.

Animals↗
PubMed1996

Intervertebral disk disease in dogs with signs of back pain alone: 25 cases (1986-1993).

OBJECTIVE: To evaluate the population characteristics, historical, clinical, and diagnostic findings; and treatment outcome of dogs with thoracolumbar intervertebral disk disease (IVDD) whose only clinical signs were those of back pain. DESIGN: Retrospective case series. ANIMALS: Dogs with IVDD and clinical signs of back pain only, without neurologic deficits, in which survey radiography of the vertebral column and diagnostic myelographic studies were performed. PROCEDURE: Review of the medical record, evaluation of survey radiographs of the vertebral column, evaluation of myelograms and estimation of apparent extent of spinal cord compression, and follow-up information provided by telephone contact with owners. RESULTS: Spinal cord compression was detected on myelography in 20 of 25 (80%) dogs. Treatment included decompressive surgery in 18 of 25 (72%) dogs and all dogs underwent intervertebral disk fenestration. The condition was improved in 24 of 25 (96%) dogs after surgery. CLINICAL IMPLICATIONS: Dogs with thoracolumbar IVDD that have clinical signs of back pain alone, without neurologic deficits, may have substantial compression of the spinal cord.

Animals↗
PubMed1996

Seizures in cats.

Seizures in cats are caused by active structural disease or secondary epilepsy. The most common structural causes are inflammatory diseases, many of which are probably viral (non-FIP) in origin. Toxoplasmosis, FIP, FeLV, and FIV are rare causes of recurrent seizures in cats. The incidence of primary epilepsy is unknown; it is unlikely to occur in domestic cats. The pattern (type and frequency) of the seizures and the age at onset of the seizures are important factors in establishing a differential diagnosis. More than 50% of cats with seizures experience nonconvulsive (mild generalized or partial complex) seizures. Though many cats experience severe cluster seizures and status epilepticus, severity of seizures is not a good predictor of outcome. Many cats stop having seizures or are controlled well with AEDs regardless of the severity of their seizure activity.

Animals↗
PubMed1995

Extramedullary hematopoiesis in the choroid plexus of five dogs.

Five dogs euthanatized because of refractory seizures were found to have hematopoietic elements in the interstitium of the choroid plexus at the level of the fourth ventricle. None of the dogs had significant hematologic or cerebrospinal fluid abnormalities. The extramedullary hematopoiesis was confined to the central nervous system and consisted of megakaryocytes, immature granulocytes, and rubricytes in two dogs and of one predominant cell population in each of the other three dogs. These findings are unique, and factors possibly contributing to the formation of a hematopoietic inductive microenvironment in the choroid plexus are cytokine-neurokine homologies, locally altered vascular supply, and aberrant functioning of bone marrow-derived central nervous system macrophages.

Animals↗
PubMed1994

Treatment of refractory generalized status epilepticus with continuous infusion of midazolam.

The optimal therapeutic approach for the patient with refractory generalized status epilepticus remains to be defined. We describe four patients with refractory generalized status epilepticus who were successfully treated with intravenous midazolam. Each patient had prolonged convulsive status epilepticus unresponsive to standard doses of intravenous benzodiazepines, phenytoin, and phenobarbital. The patients subsequently received midazolam administered as an intravenous bolus (200 micrograms/kg) followed by a continuous infusion (0.75 to 11 micrograms/kg/min) lasting 8 hours to 10 days. Clinical examination and scalp electroencephalographic monitoring documented the cessation of seizure activity within minutes of the loading dose in all patients. No significant adverse effects occurred during midazolam treatment. The one patient with prolonged midazolam infusion required fluid boluses and pressors for moderate hypotension, and the remainder of the patients safely tolerated midazolam despite preexistent hemodynamic instability. All patients recovered and maintained good seizure control. Intravenous midazolam appears to be an effective treatment for refractory generalized status epilepticus, and may represent a substantial improvement over current therapeutic approaches such as pentobarbital anesthesia.

Adult↗
PubMed1990

Pharmacokinetics of phenobarbital in the cat following multiple oral administration.

Phenobarbital was administered orally to seven healthy cats at a dose of 5 mg/kg once a day for 21 days. Serum phenobarbital concentrations were determined using a commercial immunoassay technique. A one-compartment model was used to describe the final elimination curve. The elimination half-life (t1/2 b) after the final day of treatment was 43.3 +/- 2.92 h. The large apparent volume of distribution of 695.0 +/- 43.9 mL/kg suggests that the drug was widely distributed within the body. The t1/2 b following multiple oral administration was significantly shorter than previously reported for a single oral dose of phenobarbital in the cat. Analysis of pharmacokinetic results after days 1 and 21 of treatment suggested that the elimination kinetics of phenobarbital did not change significantly with multiple oral administration. It appears that differences in elimination kinetics can exist between populations of cats. These differences emphasize the need for individual monitoring of cats receiving phenobarbital.

Administration, Oral↗
PubMed1990

Pharmacokinetics of phenobarbital in the cat following intravenous and oral administration.

Phenobarbital was administered to eight healthy cats as a single intravenous dose of 10 mg/kg. Serum phenobarbital concentrations were determined using an immunoassay technique. The intravenous data were fitted to one-, two- and three-compartment models. After statistical comparison of the three models, a two-compartment model was selected. Following intravenous administration, the drug was rapidly distributed (distribution half-life = 0.046 +/- 0.007 h) with a large apparent volume of distribution (931 +/- 44.8 mL/kg). Subsequent elimination of phenobarbital from the body was slow (elimination half-life = 58.8 +/- 4.21 h). Three weeks later, a single oral dose of phenobarbital (10 mg/kg) was administered to the same group of cats. A one-compartment model with an input component was used to describe the results. After oral administration, the initial rapid absorption phase (absorption half-life = 0.382 +/- 0.099 h) was followed by a plateau in the serum concentration (13.5 +/- 0.148 micrograms/mL) for approximately 10 h. The half-life of the terminal elimination phase (76.1 +/- 6.96 h) was not significantly different from the half-life determined for the intravenous route. Bioavailability of the oral drug was high (F = 1.20 +/- 0.120). Based on the pharmacokinetic parameters determined in this study, phenobarbital appears to be a suitable drug for use as an anticonvulsant in the cat.

Administration, Oral↗