Biomedical subjects

Peter R Patrylo

Publications and source records attributed to Peter R Patrylo.

8 recordsLinked to original sources

PubMed2007

Anatomic and electrophysiologic evidence for a proconvulsive circuit in the dentate gyrus of reeler mutant mice, an animal model of diffuse cortical malformation.

Although cortical malformations (CMs) are often associated with epilepsy, the underlying mechanisms are unknown. The reeler mouse is a model of CM with enhanced susceptibility to epileptiform activity, including the in vitro dentate gyrus, a region normally resistant to seizures. In this study, field potential recordings in hippocampal slices and the Timm stain were used to examine mossy fiber distribution in the dentate gyrus. In artificial cerebrospinal fluid containing bicuculline, 100% of reeler slices and 0% of control slices had spontaneous and antidromic evoked prolonged negative field potential shifts that were blocked by glutamate receptor antagonists. Sections from reeler mice, but not controls, exhibited a dark band of Timm's stain at the molecular layer/granule cell layer border. These data reveal that mossy fiber distribution is altered in reeler mice and coincides with the presence of an abnormal proconvulsive glutamatergic circuit.

Action Potentials↗

PubMed2006

Glucose metabolites in the striatum of freely behaving rats following infusion of elevated potassium.

The outcome of patients with traumatic brain injury (TBI) can be predicted by the extracellular potassium concentration and the change in energy homeostasis. In this study, the authors investigated the effects of high potassium concentrations on extracellular levels of glucose, pyruvate and lactate in the rat striatum. Applying artificial cerebrospinal fluid (ACSF) enriched with 120 mM potassium by reverse microdialysis leads to an increase in lactate and reduction in glucose and pyruvate. Consequently, the lactate to pyruvate ratio was also increased. These data are discussed in the context of recent studies on lactate/pyruvate conversion and the potential mechanisms whereby high potassium could affect this equilibrium. We conclude that ischemic-like events are unlikely to explain these K(+)-induced changes.

Animals↗

PubMed2006

Reeler mutant mice exhibit seizures during recovery from isoflurane-induced anesthesia.

Reeler mice are a model of cortical malformation with enhanced seizure susceptibility. Data suggest that the propensity to anesthesia-induced seizures may be enhanced in animal models with developmental anomalies. Consequently, reeler mice were monitored behaviorally before, during and after isoflurane anesthesia. During recovery, 12% of reeler homozygotes had class I/II seizures while the remaining 88% exhibited convulsive seizures entailing opisthotonus and forepaw drumming. Similar behavior was not observed in controls. These data reveal that reeler mice display isoflurane-induced seizures and provide support for the hypothesis that developmental anomalies may predispose the central nervous system to anesthesia-induced seizures.

Anesthetics, Inhalation↗

PubMed2006

Reeler homozygous mice exhibit enhanced susceptibility to epileptiform activity.

PURPOSE: Seizures are observed frequently in humans with diffuse neuronal migration disorders. The reeler mutant mouse also exhibits a diffuse disruption of migration, yet no pro-epileptic phenotype has been reported for this model. Whether this disparity reflects a phenotypic difference that can be used to delineate the mechanisms associated with increasing seizure susceptibility or reflects a paucity of knowledge is unclear. Consequently, this study examined whether seizure susceptibility is altered in reeler mutant mice. METHODS: In vivo (minimal electroshock delivered transcorneally) and in vitro techniques (field-potential recordings in neocortical and hippocampal brain slice preparations exposed to bicuculline methiodide) were used to determine whether the susceptibility to epileptiform activity is enhanced in reeler homozygous mice relative to controls. Adult (3-7 months) male reeler homozygotes (rl/rl) and controls (+/?) were identified based on their behavioral phenotype and were used in all experiments. RESULTS: Minimal electroshock revealed that rl/rl mice, compared with controls, exhibited a lower threshold for electroshock-induced seizures (4.5 +/- 0.52 vs. 6.7 +/- 0.35 mA), and a higher incidence of behavioral seizures (median seizure score, class 4 vs. class 0) when animals were subjected to a 5-mA electroshock stimulus. Additionally, neocortical and hippocampal slices from rl/rl mice were more likely to generate spontaneous epileptiform activity after bicuculline application, compared with controls, and the duration of the epileptiform events elicited in 10-30 muM bicuculline was longer in slices from rl/rl mice. CONCLUSIONS: These data demonstrate that rl/rl mice have enhanced seizure susceptibility that is in part intrinsic to the malformed neocortex and hippocampus. Thus in contrast to prior belief, most animal models of diffuse neuronal migration disorders do exhibit a pro-epileptic phenotype.

Animals↗

PubMed2005

Basic research in epilepsy and aging.

A PubMed search of the years 1965 to 2003 found only 30 articles that were directly related to modeling seizures or epilepsy in aged animals. This lack of research is disturbing but explainable because of the high cost of aged animals and their increasing infirmity. Many changes occur in the older brain: cell loss in the hippocampal formation, changes in long-term potentiation maintenance, alteration in kindling, increased susceptibility to status epilepticus, and neuronal damage from stroke. The effect of aging on voltage-gated sodium and calcium channels has not been studied sufficiently. With increasing numbers of elderly persons with epilepsy needing appropriate treatment, the need to better understand the basic mechanisms of epilepsy is crucial.

Aged↗

PubMed2005

Correlations between granule cell physiology and bioenergetics in human temporal lobe epilepsy.

Human temporal lobe epilepsy (TLE) is associated with bioenergetic abnormalities including decreased phosphocreatine (PCr) normalized to ATP. The physiological consequences of these metabolic alterations have not been established. We hypothesized that impaired bioenergetics would correlate with alterations in physiological functions under conditions that strongly activate neural metabolism. We correlated several physiological variables obtained from epileptic human dentate granule cells studied in slices with hippocampal PCr/ATP measured using in vivo magnetic resonance spectroscopy. The physiological variables included: the ability to fire multiple action potentials in response to single stimuli, the inhibitory postsynaptic potential (IPSP) conductance and the responses to a 10 Hz, 10 s stimulus train. We noted a significant negative correlation between the ability to fire multiple spikes in response to single synaptic stimulation and PCr/ATP (P < 0.03) and a positive correlation between the IPSP conductance and PCr/ATP (P < 0.05). Finally, there was a strong correlation between PCr/ATP and the recovery of the membrane potential following a stimulus train (P < 0.01), with low PCr/ATP being associated with prolonged recovery times. These data suggest that the bioenergetic impairment seen in this tissue is associated with specific changes in excitatory and inhibitory neuronal responses to synchronized synaptic inputs.

Adenosine Triphosphate↗

PubMed2004

Aging alters electroencephalographic and clinical manifestations of kainate-induced status epilepticus.

PURPOSE: The elderly exhibit an increased risk for developing status epilepticus and status-related morbidity and mortality. However, it is unclear how aging alters the progression of electroencephalographic (EEG) activity and behavioral manifestations during status epilepticus. METHODS: A repetitive low-dose kainate treatment protocol (2.5 mg/kg/h; i.p.) was used in this study in conjunction with EEG and behavioral monitoring from freely behaving adult (7-8 months) and aged (22-25 months) Fischer 344 rats to assess the effects of aging on status epilepticus. RESULTS: During kainate treatment, both groups exhibited an increase in EEG power that corresponded with the time course of kainate treatment. However, visual inspection and spectral analysis revealed a reduction of the faster frequencies (12.5-35 Hz) in the EEGs of aged rodents. A similar progression of behavioral manifestations was observed in adult and aged rodents during kainate treatment, although the frequency of preseizure manifestations (e.g., wet-dog shakes; aged rats, 110 events/h vs. adults, 25 events/h; median values) was greater, and latency to onset for any given behavioral manifestation (e.g., class V seizures; aged median, 60 min, vs. adult median, 145 min) was consistently shorter within the aged group. CONCLUSIONS: These data reveal that aged Fischer 344 rats exhibit altered EEG activity (reduction of higher frequencies) and clinical manifestations during kainate-induced status epilepticus. Taken together, these data indicate an age-related change in seizure onset and spread after exposure to glutamate analogues.

Age Factors↗

PubMed2003

Physiology of human cortical neurons adjacent to cavernous malformations and tumors.

PURPOSE: Focal neocortical seizures can be associated with a number of specific pathologies including supratentorial tumors and cavernous malformations (CMs), both of which are highly epileptogenic. METHODS: To begin to address the question of whether these lesions have different mechanisms of epileptogenesis, we used intracellular recordings from neurons adjacent to intracerebral neoplasms and cerebral CMs. Developmental anomalies were not included in this study. RESULTS: Neurons adjacent to CMs had a greater propensity to show large (>5 mV), complex spontaneous synaptic events than did neurons neighboring neoplastic substrates (50 vs. 4.7% of cells and 75 and 8% of patients, respectively; p < 0.004; p < 0.05). Both spontaneous excitatory and inhibitory events were noted. In contrast, in tissue adjacent to tumors, low-amplitude (<3 mV) spontaneous excitatory activity predominated. Neurons neighboring CMs also exhibited more excitable responses to synaptic stimulation, with multiple action potentials riding on prolonged excitatory postsynaptic potentials (EPSPs) being evoked in 71% of these cells, versus 32% of cells from the tumor group; p < 0.05. In studies using hippocampal tissue, we noted a similar pattern of spontaneous activity in tissue adjacent to CMs. CONCLUSIONS: These data suggest that CMs may induce seizure activity via a different pathophysiologic mechanism(s) than glial tumors.

Adolescent↗