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J E Penny

Publications and source records attributed to J E Penny.

16 recordsLinked to original sources
PubMed1992

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↗
PubMed1988

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↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1984

Scanning electron microscopy of the cochlea in rats with Streptococcus pneumoniae otitis media.

This investigation was performed to determine the morphologic effects of bacterial otitis media on the organ of Corti. The middle ear cavities of rats were inoculated with Streptococcus pneumoniae or saline and the animals were killed on days 1, 4, 7, 10, 14, and 21 after inoculation. Middle ear cultures were obtained and the cochleas were examined using scanning electron microscopy. All animals killed on day 1 had positive cultures, but by day 21, all cultures were negative. Cochlear changes observed were (1) damage to supporting cells (Deiters' cells), (2) morphologic changes of hair cell stereocilia, and (3) loss of inner and outer hair cell stereocilia and cell bodies (to a lesser extent), especially in the lower middle and basal turns. These changes appeared to occur in a definite sequence; ie, damage to the supporting cells, changes in stereocilia, and, finally, hair cell loss. These data show that cochlear damage and hair loss can be associated with bacterial otitis media.

Animals↗
PubMed1984

Impairment in cochlear function produced by chloramphenicol and noise.

Ototoxic interaction between chloramphenicol and noise was studied in two separate investigations. In the first study, permanent ototoxicity was demonstrated in a group of rats which were subjected to short-duration, high-intensity noise and were then given chloramphenicol orally. The anatomical damage in this group was consistent with observed changes in cochlear round window recordings of cochlear microphonics at 4 kHz and of the N1 component of the eighth nerve action potential. In the second study, a temporary depression in the function of the cochlea was observed in rats subjected to the noise-chloramphenicol regimen used in the first study. Depressions in recordings of the round window similar to those in the first study were seen only during the first five days of recordings. After the fifth day, the recordings of the round window were normal, indicating recovery from a temporary shift in threshold produced by chloramphenicol and noise. Incidence of purulent otitis media was found in 57 and 0% of the animals in the first and second studies, respectively. The combination of chloramphenicol and noise appears to be responsible for the production of temporary cochlear deficits. The addition of the third variable, otitis media, appears to result in permanent impairment of the cochlea.

Animals↗
PubMed1982

Cytoarchitectural and dendritic patterns of the dorsal column nuclei of the opossum.

Cytoarchitectural and dendritic patterns of dorsal column nuclei of the opossum, Didelphis marsupialis virginiana, were studied with Nissl and Golgi preparations. Two basic cell types, round cells and irregular cells, are found. Round cells have a large, round cell body (20-30 mu) with a distinct nucleolus in the nucleus. The cytoplasm is fine, evenly dispersed Nissl material with occasional tigroid bodies. Irregular cells have triangular, multipolar or fusiform cell bodies (8-10 mu) with indistinct nucleus and nucleolus. Three cellular regions differentiate the rostrocaudal axis of the nucleus cuneatus: (1) rostral region (2) obex region and (3) caudal region. These regions are distinguishable on the basis of round cell arrangements, total cell populations, and round cell to irregular cell ratios. In contrast, two cytoarchitecturally distinct regions occur along the rostrocaudal region of the nucleus gracilis: (1) a rostral region and (2) a caudal region. Round cells have a sparse dendritic arrangement of a multiplanar, radiate type. Round cells forming small clusters are arranged as if on the surface of an imaginary sphere with at least one dendrite from each cell radiating toward the center of this sphere. Only fusiform irregular cells were observed with Golgi stains and their cell bodies exhibited a polar, radiating dendritic pattern. Dense dendritic arborizations are observed in the obex region of both gracile and cuneate nuclei.

Animals↗
PubMed1981

Structural diversity of marginal (lamina I) neurons in the adult monkey (Macaca mulatta) lumbosacral spinal cord: a golgi study.

Utilizing the Golgi technique, the present study provides a structural analysis of primate marginal (lamina I) neurons in the lumbosacral spinal cord. Marginal neurons are classified on the basis of major structural differences in dendritic conformation, distribution, and specialization. Cell size and shape alone were not found to be reliable criteria. Marginal cells can be divided into four major groups. Group I (Aspiny Neurons with Thick, Blunt Dendrites) consists of neurons with relatively thick dendrites which have an abrupt, blunt termination and few spines. This heterogeneous group includes large, medium, and small neurons of various shapes. Group II cells (Large to Medium Spiny Neurons) can be subdivided into two distinct groups: Group IIA neurons, which have longitudinal spiny dendritic arbors, and Group IIB cells, which have a moderately spiny, fan-shaped dendritic arbor which spreads across the lateral portion of the dorsal marginal zone. Both Groups A and B exhibit several types of spines. Group III (Aspiny Neurons with Thin, Tapering Dendrites) consists of small to medium size neurons which can be further divided into two groups: Group IIIA, which is characterized by oval- to fusiform-shaped neurons with tortuous, fine, tapered dendrites which ramify in the dorsolateral fasciculus and the lateral funiculus, and Group IIIB, which is composed of fusiform-pyramidal-and polygonal-shaped neurons with fine, tapering dendrites confined to lamina I. Group IV (Small Spiny Neurons) are characterized by a small fusiform- to pyramidal-shaped cell body and delicate longitudinal dendrites with small, short-necked pedunculated spines. This group is subdivided into Group IVA cells, which are found within lamina I proper and Group IVB cells, which are located in the dorsolateral fasciculus and have unmyelinated axons. The present study demonstrates considerably more structural diversity within the marginal zone than has been previously reported, and offers sufficient variation to correlate with functional differences described from laminal I neurons.

Animals↗
PubMed1981

Ototoxic drugs and noise.

Drugs that produce tinnitus can be subdivided into those which produce temporary or permanent hearing loss and those which apparently do not cause any hearing loss. The tinnitus occurring with drugs of the first group is probably secondary to the hearing loss. However, most of the drugs that produce tinnitus without an accompanying hearing loss probably do so because of their effect on biogenic amines in the central nervous system and/or as an extension of their proconvulsant side-effects. A pre-existing cochlear impairment is the underlying factor in most patients who experience tinnitus. Not only can ototoxic drugs or high levels of noise produce cochlear impairment but the interaction of the two can place humans in more jeopardy than when exposed to either agent alone. Chloramphenicol has little ototoxic potential when administered systemically in humans. However, our studies show that when chloramphenicol is combined with noise exposure in rats, considerably more cochlear damage results than from the noise alone (chloramphenicol alone does no produce any cochlear damage). We are presently conducting more detailed studies of this ototoxic interaction to determine whether it occurs with other antibiotics (such as erythromycin) which are also commonly considered to have minimal ototoxicity.

Acoustic Stimulation↗
PubMed1980

A comparison of cochlear microphonics and N1 in audiogenic-seizure-susceptible and control rats.

Although numerous studies have shown that cochlear impairment exists in audiogenic-seizure (AGS)-susceptible mice, there is only one report of cochlear potentials obtained from AGS-susceptible rats. To investigate the hypothesis that cochlear impairment also exists in AGS rats, cochlear microphonics (CM) and the primary afferent activity of the auditory division of the eighth cranial nerve (N1) were studied in AGS rats. AGS rats were obtained from the Veterans Administration Medical Center (Shreveport, La.) colony of Sprague Dawley derived animals, and control rats were obtained from Sprague Dawley, Inc. Two school bells ringing simultaneously were used to produce a sound of approximately 115 dB (AGS test stimulus). Exposure to the AGS test stimulus was once per week for three consecutive weeks. Chloramphenicol was used to treat the frequent otitis media found in the colony of AGS rats. Two categories of AGS-susceptible and control rats were studied: (1) rats exposed to the AGS test stimulus and chloramphenicol regimen; and (2) rats not receiving these treatments. All rats were anesthetized with i.p. Dial-Urethane and prepared for cochlear round window recording. Cochlear microphonics were recorded in response to a click stimulus. A significant decrease in cochlear sensitivity was seen in both groups of AGS rats when compared to appropriate controls as reflected by a 25-35 dB shift in all CM and N1 input-output functions. These results support the hypothesis that a functional cochlear impairment exists in the AGS rat.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗
PubMed1975

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↗
PubMed1975

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↗
PubMedDate not supplied

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↗
PubMedDate not supplied

Cochlear morphology of the audiogenic-seizure susceptible (AGS) or genetically epilepsy prone rat (GEPR).

The organ of Corti (OC) of the genetically epilepsy prone rat (GEPR), a strain which is highly susceptible to audiogenic seizures (AGS), was examined by means of the scanning electron microscope (SEM). Ten female GEPRs (seizure intensity score of 2 or 3) and 10 female control rats (seizure intensity score of 0) were used in this study. (Seizure intensity was scored on an ascending scale of 0-9; 0 being no seizure (Jobe et al., 1973).) Each rat was perfused with buffered glutaraldehyde and the temporal bones fixed for one week in formalin. After decalcification, staining and microdissection, the entire OC was prepared for scanning electron microscopy (SEM). The GEPR organ of Corti contained several morphological differences when compared with controls. 1) In all 10 GEPRs, the headplates forming the top of the tunnel of Corti exhibited some form of structural abnormality. 2) Five animals had some form of stereocilia aberration of the inner (IHC) and/or outer (OHC) hair cells. 3) In 4 animals, significant numbers (10-15%) of IHC's were missing in large segments of all cochlear turns. 4) In 2 GEPRs, all OHC's were absent from the middle turn to the hook. In these 2 animals, IHC's were present in the upper middle turn but became less numerous and completely absent in the basal turn and hook. 5) One set of cochleas had 1000 more OHC's than had those of control rats. Since GEPRs are genetically susceptible to seizures, the preceding cochlear abnormalities are probably genetically-induced developmental defects. It is likely that the abnormally long stereocilia, mis-shaped stereocilia and deficits in hair cell populations are a consequence of the distorted headplates. The elongated stereocilia could be a compensatory attempt to contact the tectorial membrane during development. The mis-shaped stereocilia and hair cell deficits could represent a failure of compensatory mechanisms. The cochlear abnormalities may play a role in both susceptibility and intensity of audiogenic seizures.

Acoustic Stimulation↗