Developmental and genetic audiogenic seizure models: behavior and biological substrates.

Audiogenic seizure (AGS) models of developmental or genetic origin manifest characteristic indices of generalized seizures such as clonus or tonus in rodents. Studies of seizure-resistant strains in which AGS is induced by intense sound exposure during postnatal development provide models in which other neural abnormalities are not introduced along with AGS susceptibility. A critical feature of all AGS models is the reduction of neural activity in the auditory pathways from deafness during development. The initiation and propagation of AGS activity relies upon hyperexcitability in the auditory system, particularly the inferior colliculus (IC) where bilateral lesions abolish AGS. GABAergic and glutaminergic mechanisms play crucial roles in AGS, as in temporal lobe models of epilepsy, and participate in AGS modulatory and efferent systems including the superior colliculus, substantia nigra, basal ganglia and structures of the reticular formation. Catecholamine and indolamine systems also influence AGS severity. AGS models are useful for elucidating the underlying mechanisms for formation and expression of generalized epileptic behaviors, and evaluating the efficacy of modern treatment strategies such as anticonvulsant medication and neural grafting.

Amniotic fluid indices of fetal pulmonary maturity with preterm premature rupture of membranes.

OBJECTIVE: To evaluate the performance of the TDx/TDxFLx fetal lung maturity II assay (Abbott Laboratories; Abbott Park, IL) on amniotic fluid (AF) specimens collected vaginally from women with preterm premature rupture of membranes (PROM). METHODS: We reviewed charts of patients with preterm PROM treated at Shands Hospital at the University of Florida from January 1, 1995, to June 30, 1999. Negative predictive values (prediction of the absence of neonatal respiratory distress) of mature (at or above 55 mg/g) and borderline (40-54 mg/g) test results were calculated for 153 women. RESULTS: Respiratory distress syndrome (RDS) occurred with frequencies of one in 42 and three in 29 cases with mature and borderline test results, respectively. All cases of RDS were mild, defined as sustained tachypnea with or without need for supplemental oxygen. With an immature (less than 40 mg/g) test result, 20 of 82 infants developed RDS, and half of those cases were severe, defined as needing mechanical ventilation. Negative predictive values of mature and borderline tests were 97.6% (95% confidence interval [CI] 92.9, 100) and 89.7% (95% CI, 78.3, 100), respectively. CONCLUSION: Mature results from fetal lung maturity tests of vaginally collected AF predict the absence of RDS with a high degree of accuracy.

Anti-epileptiform effects of audiogenic seizure priming on in vitro kindling in rat hippocampus.

The effect of priming for audiogenic seizures (AGS) on the development of epileptiform activity in the hippocampus was studied using in vitro kindling (IVK) in Long-Evans rats. AGS priming consists of intense auditory stimulation during a critical period of auditory development, resulting in sound-induced clonic convulsions upon subsequent testing. Between postnatal day (PND) 28 and 50, slices from subjects primed and sham-primed for AGS on PND 18 were used for recording responses in area CA1 of hippocampus following Schaffer collateral stimulation from stratum radiatum of area CA2/CA3. The developmental priming procedure, which enhances auditory brainstem excitability, resulted in fewer afterdischarges in slices from primed subjects across initial IVK stimulation sequences. These results suggest that changes in excitability that occur with acoustic priming can initially diminish selective epileptiform response characteristics in forebrain areas such as the hippocampus.

Latency alterations of the auditory brainstem response in audiogenic seizure-prone Long-Evans rats.

Audiogenic seizure susceptibility in the normally seizure-resistant Long-Evans rat may result from altered processing in the auditory pathway. Representative waveform latencies of the auditory brainstem responses (ABR) were recorded to examine generator alterations at different levels of the auditory neuraxis. Male Long-Evans rats primed for audiogenic seizures (AGS) on PND 14 with a 10 kHz pure tone at 120 dB SPL for 8 min were tested for AGS on PND 28 with 120 dB SPL continuous white noise. Primed subjects displayed wild running culminating in clonic convulsions. Following behavioral testing at 4-6 months, vertex recordings of ABR waves Ia-VI were made in anesthetized subjects using pure tone stimulus bursts. AGS subjects showed marginally elevated ABR thresholds. Shorter ABR wave latencies were elicited in AGS subjects for peripheral and central auditory components with stimulus intensities above 50 dB PeSPL at 8 and 40 kHz. Interpeak intervals were reduced for waves Ia-V and III-V in AGS subjects. These results reveal that intense sound stimulation during a sensitive period of development later reduces processing time at higher intensity levels.

Audiogenic seizures in the developmentally primed Long-Evans rat.

The Long-Evans rat is a hybrid rodent strain with little innate susceptibility to audiogenic seizures (AGS). The present study examines parameters of acoustic priming (induced susceptibility) and testing for AGS during postnatal development subsequent to auditory function, and identifies the effects of stimulus intensity, repeated testing, and gender upon AGS activity. Rats were exposed to 125-dB SPL 10-kHz tone bursts at 14-36 days of age and tested with white noise at 14 or 19 days following sound exposure. All priming/testing combinations yielded AGS susceptibility; animals primed at 18 days showed the highest incidence of clonic seizures when tested 14 days later. All subjects displayed clonus at testing intensities of 120 dB, although some seizure behaviors could be elicited at 100 dB. Repeated testing at 120 dB increased latency to clonus and clonus duration, and total wild running activity. Gender differences for AGS expression were minimal. These results demonstrate the viability of the seizure-resistant Long-Evans rat for study of AGS.

Estrogen treatment and age effects on auditory brainstem responses in the post-breeding Long-Evans rat.

The auditory brainstem response (ABR) was recorded from 20-month-old Long Evans hooded female rats to determine if latency reductions occur from estrogen replacement. The ABR in these post-breeding age rats was also examined for reductions in response latencies as a function of adult age. Tone pip stimuli (8 and 40 kHz) were presented at 21, 51, or 81 s(-1). Aging control and ovariectomized animals showed slower response latencies for waves Ib-VI than young adults for 8 and 40 kHz stimulation at 21 s(-1). Increased stimulus rate resulted in longer latencies for all waves at 20 months. In contrast to hormone treatment effects in young adults, ABR latencies in post-breeding age estrogen-treated animals were not reduced, consistent with a general decrease in CNS responsiveness to estrogen steroids associated with age. The results also suggest that sensorineural modifications in the auditory system which prolong ABR latencies can occur early in the aging process of adult female subjects.

Tectal graft modulation of audiogenic seizures in Long-Evans rat.

Audiogenic seizure (AGS) activity can be induced in the seizure-resistant Long-Evans rat by postnatal priming. This study examined the effects of unilateral lesions of the inferior colliculus (IC) and implantation of tectal grafts on AGS components. Animals were primed with a 10-kHz tone burst at 120 dB on postnatal day 14 and tested for AGS susceptibility on day 28, and then two groups were unilaterally lesioned including animals receiving embryonic day 16-17 grafts of caudal tectum. Subsequently, animals were repeatedly tested for wild running and clonic-tonic convulsion components of AGS. The results demonstrate that unilaterally grafted animals with partial IC lesions showed significant reduction in the incidence of clonus expression with greater terminal uniphasic wild running behavior. These effects were stronger than in animals with comparable unilateral lesions alone. Many neurons in graft cases were in direct contact with host tissues to provide a substrate for tissue interactions previously demonstrated to promote neuron survival and remediate IC functions.