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J E Penny

Publications and source records attributed to J E Penny.

9 recordsLinked to original sources

Serotonergic abnormalities in the central nervous system of seizure-naive genetically epilepsy-prone rats.

Seizure predisposition in Genetically Epilepsy-Prone Rats (GEPRs) is characterized by abnormal sensitivity to a number of seizure provoking stimuli. The GEPR model is composed of two independently derived colonies with each exhibiting a characteristic convulsive pattern. In response to a standardized sound stimulus, GEPR-3s exhibit moderate or clonic convulsions while GEPR-9s exhibit more severe tonic extensor convulsions. In order to further characterize the neurochemical abnormalities that underlie seizure predisposition in GEPRs, the current study examined serotonin concentrations in 14 discrete brain areas of controls, GEPR-3s and GEPR-9s. In all areas examined, serotonin concentrations were lower in either one or both GEPR types than in seizure resistant controls. In 6 of the 14 areas both GEPR-3s and GEPR-9s had levels significantly lower than controls. In an additional 7 areas GEPRs had serotonin concentrations of similar magnitude which were significantly lower than control when the GEPR values were combined. In cerebellum, GEPR-3s had significantly lower serotonin concentration than either controls of GEPR-9s while in the striatum, GEPR-9s had significantly lower serotonin levels than either GEPR-3s or controls. In summary, GEPRs have widespread deficits in serotonin concentration and that these abnormalities appear to contribute to the seizure predisposition that characterizes these animals.

Animals

Effects of cisplatin and thiosulfate upon auditory brainstem responses of guinea pigs.

Two side effects which limit the use of cisplatin in cancer chemotherapy are severe nephrotoxicity and ototoxicity. The concurrent administration of sodium thiosulfate with cisplatin reportedly protects from cisplatin nephrotoxicity, however, protection from ototoxicity has not been documented. The purpose of this study was to examine the efficacy of using thiosulfate to ameliorate the ototoxic effects of cisplatin. Toward this end, the effects of cisplatin alone, cisplatin administered concurrently with sodium thiosulfate (CIS/THIO), and sodium thiosulfate alone on the auditory brainstem response (ABR) of guinea pigs were compared. ABR waveforms, comparing latencies, amplitudes and response thresholds, were monitored before, immediately after, and 30 days post treatment. Sodium thiosulfate administered with cisplatin (CIS/THIO) consistently protected animals from hearing loss and surprisingly yielded significant increases in amplitude when compared to baseline and saline controls. However, ABRs of CIS/THIO animals returned toward baseline values after 30 days.

Animals

Auditory aspects of seizure in the genetically epilepsy prone rat.

The organ of Corti of Genetically Epilepsy Prone Rats was examined anatomically and electrophysiologically using scanning electron microscopy (SEM) and electrophysiological recording of alternating current cochlear potentials (ACCP) and N1, a volume conductor recording of the primary auditory afferent action potentials. ACCPs for GEPRs with low intensity seizures (Acoustic Response Score (ARS) = 2 or 3) and high intensity seizures (ARS = 9) showed similar impairment in cochlear function. Approximately a 25-35 dB shift in input-output functions was present in GEPRs as compared to controls. SEM revealed several types of possible genetic abnormalities which explain the deficits in cochlear function and could serve as the basis for seizure predisposition in these animals.

Acoustic Stimulation

Link between functional and morphological changes in the inner ear--functional changes produced by ototoxic agents and their interactions.

Common potentials used to evaluate cochlear function are the ac cochlear potential (ACCP), N1 and the positive dc endocochlear potential (EP). The ACCP is an electrical analogue of the sound stimulus; its source is the electrical activity of the cochlear hair cells. N1 is a volume conductor recorded action potential of the auditory nerve. The EP is the positive polarization of the middle compartment of the cochlea (scala media) with respect to the other compartments (the scalae tympani and vestibuli); the stria vascularis is apparently responsible for the EP. Generally, ototoxic drugs and very intense broad-band noise affect the basal portion of the cochlea first and, because of tonotopic organization, the ACCP responses to high frequency pure tones are affected before those to the low frequencies. However, the correlation between the effect of an ototraumatic agent on the ACCP and its effect on cochlear morphology is not always reliable. The correlations between changes in N1 and EP and in cochlear morphology are even less precise. Also discussed will be the cochlear effects of noise and the ototoxic interactions between drug/drug, noise/drug, and noise/drug/otitis media.

Acetylcysteine

Quantitative oxidative enzyme histochemistry of the spinal cord. Part 1. Distribution of enzyme activity in anterior horn cells.

Cytophotometric measurements of the activities of 5 oxidative enzymes (succinate, malate, lactate, NAD+-linked isocitrate and NADH dehydrogensases) have been made in anterior horn cells of the lumbar and cervical spinal cord of the rabbit. The thickness of tissue sections was measured by an interference microscope and various optical and chemical precautions were taken to diminish the possible errors that might be involved in cytophotometry. The findings of the study indicated a unimodal distribution of the activities of all of the enzymes studied in anterior horn cells, though there was a wide range of enzyme concentration among different cells. Thus the findings in the rabbit are consistent with the "constant proportion" hypothesis of the activity of certain oxidative enzymes, and are contrary to a previous finding that there may be two populations of succinate dehydrogenase-containing anterior horn cell.

Animals

Quantitative oxidative enzyme histochemistry of the spinal cord. Part 2. Relation of cell size and enzyme activity to vulnerability to ischaemia.

Cytophotometric measurements of the activities of 5 enzymes (succinate, malate, and NAD+-linked isocitrate dehydrogenases from the tricarboxylic cycle, lactate dehydrogenase from the Embden-Meyerhof pathway, and NADH dehydrogenase) were correlated with cell volume for neurones in the anterior horn of rabbit lumbar and cervical spinal cord. The data for succinate and isocitrate dehydrogenases indicated that these enzymes were at higher concentrations in the smaller neurones, which consist largely of interneurones. No preferential localization to particular sizes of cell could be assigned to the other enzymes studied. The relationship between enzyme distribution patterns and their possible role in contributing toward susceptibility to ischaemia of particular sizes of neurones is discussed.

Animals

Noradrenergic abnormalities in the central nervous system of seizure-naive genetically epilepsy-prone rats.

Norepinephrine (NE) concentrations were measured in 15 discrete areas of the central nervous system of two types of genetically epilepsy-prone rats (GEPRs) and in nonepileptic controls. Both moderate-seizure (GEPR-3) and severe-seizure (GEPR-9) animals had extensive abnormalities in brain NE concentration. Deficits of equal magnitude in GEPR-3s and GEPR-9s were found in the spinal cord, midbrain minus the inferior colliculus, inferior colliculus, hypothalamus, amygdala, hippocampus, occipital + parietal cortex, frontal cortex, and olfactory septum. Because both types of GEPRs share these deficits and share seizure susceptibility, we hypothesize that these areas are candidates for regulation of seizure susceptibility in GEPRs. In addition, because GEPR-9s have more severe seizures than GEPR-3s and because GEPR-9s had greater NE deficits in several brain areas (cerebellum, pons-medulla, thalamus, and possibly the temporal cortex and olfactory bulbs), we hypothesize that these areas may be important in regulation of seizure severity in GEPRs. All animals used in these experiments had been protected from seizure-provoking stimuli and were naive to seizures. Because the abnormalities in NE concentration were present in seizure-predisposed animals that were protected from seizures, we conclude that these abnormalities are important components of the seizure-predisposition characteristic of GEPRs and do not result from seizure experience.

Acoustic Stimulation