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Structural changes in limbic regions are often observed in individuals with temporal lobe epilepsy (TLE) and in animal models. However, the brain structural changes during the evolution into epilepsy remain largely unknown. Therefore, the purpose of this study was to define the temporal changes in limbic structures after experimental status epilepticus (SE) during the latency period of epileptogenesis in vivo, with quantitative diffusion tensor imaging (DTI) and T2 relaxometry in an animal model of chronic TLE. A pair of fifty micron electrodes was implanted into the ventral hippocampus in twelve male adult rats. Self-sustaining SE was induced with electrical stimulation in eleven rats. Three rats served as age-matched controls. In vivo diffusion tensor and T2 magnetic resonance imaging (MRI) was performed at 11.1 Tesla, pre- and post-implantation of electrodes and 3, 5, 7, 10, 20, 40 and 60 days post-SE to assess structural changes. Spontaneous seizures were identified with continuous time-locked video-monitoring. Following imaging in vivo, fixed, excised brains were MR imaged at 17.6 Tesla. Subsequently, histological analysis was correlated with MRI results. Following SE, 8/11 injured rats developed spontaneous seizures. Unique to these 8 rats, early T2, diffusivity and anisotropy changes were observed in vivo within the parahippocampal gyrus (contralateral) and fimbria (bilateral). In excised brains, bilateral increase in anisotropy was observed in the dentate gyrus, corresponding to mossy fiber sprouting as determined by Timm staining. Using T2 relaxometry and DTI, specific transient and long-term structural changes were observed only in rats that developed spontaneous limbic seizures.

We have previously reported preictal spatiotemporal transitions in human mesial temporal lobe epilepsy (MTLE) using short term Lyapunov exponent (STL max ) and average angular frequency (\( \Omega \) ). These results have prompted us to apply the quantitative nonlinear methods to a limbic epilepsy rat (CLE), as this model has several important features of human MTLE. The present study tests the hypothesis that preictal dynamical changes similar to those seen in human MTLE exist in the CLE model. Forty-two, 2-hr epoch data sets from 4 CLE rats (mean seizure duration 74±20 sec) are analyzed, each containing a focal onset seizure and intracranial data beginning 1 hr before the seizure onset. Three nonlinear measures, correlation integral, short-term largest Lyapunov exponent and average angular frequency are used in the current study. Data analyses show multiple transient drops in STL max values during the preictal period followed by a significant drop during the ictal period. Average angular frequency values demonstrate transient peaks during the preictal period followed by a significant peak during the ictal period. Convergence among electrode sites is also observed in both STL max and \( \Omega \) values before seizure onset. Results suggest that dynamical changes precede and accompany seizures in rat CLE. Thus, it may be possible to use the rat CLE model as a tool to refine and test real-time seizure prediction, and closed-loop intervention techniques.

Analysis of intracranial electroencephalographic (iEEG) recordings in patients with temporal lobe epilepsy (TLE) has revealed characteristic dynamical features that distinguish the interictal, ictal, and postictal states and inter-state transitions. Experimental investigations into the mechanisms underlying these observations require the use of an animal model. A rat TLE model was used to test for differences in iEEG dynamics between well-defined states and to test specific hypotheses: 1) the short-term maximum Lyapunov exponent (STL(max)), a measure of signal order, is lowest and closest in value among cortical sites during the ictal state, and highest and most divergent during the postictal state; 2) STL(max) values estimated from the stimulated hippocampus are the lowest among all cortical sites; and 3) the transition from the interictal to ictal state is associated with a convergence in STL(max) values among cortical sites. iEEGs were recorded from bilateral frontal cortices and hippocampi. STL(max) and T-index (a measure of convergence/divergence of STL(max) between recorded brain areas) were compared among the four different periods. Statistical tests (ANOVA and multiple comparisons) revealed that ictal STL(max) was lower (p0.05) than other periods, STL(max) values corresponding to the stimulated hippocampus were lower than those estimated from other cortical regions, and T-index values were highest during the postictal period and lowest during the ictal period. Also, the T-index values corresponding to the preictal period were lower than those during the interictal period (p0.05). These results indicate that a rat TLE model demonstrates several important dynamical signal characteristics similar to those found in human TLE and support future use of the model to study epileptic state transitions.

A total of 32 microwire electrodes were implanted bilaterally into the hippocampus of Sprague-Dawley rats, which were then stimulated in the manner prescribed for the chronic limbic epilepsy model. After the initial seizure brought on by the stimulation, the animals were recorded at a high sampling rate (approximately 12 kHz) for the entire duration of the latent period. Coherence was calculated across channels in both stimulated (and later seizing) animals and non-stimulated (and thus non-seizing control) animals. Average coherence over time was greatest in intrahemispherical electrode pairs in both stimulated and non-stimulated animals. However, the 200-800 Hz band displays increased coherence interhemispherically and up to 200 Hz band displays decreased coherence interhemispherically: this occurs only in stimulated animals.

Recently a number of groups [1,2] have reported on the existence of pathological High frequency oscillations (HFO's) (oscillations in the frequency range of 80–200 Hz, termed as Ripple band and oscillations in the frequency range of 200 Hz and above, termed as Fast Ripple band) in the epileptic brain both in in-vivo and in-vitro experiments. Our goal in this study is to study the statistical modulation of HFOs during epileptogenesis in order to characterize their function in progression to seizures in the epileptic brain. In this study we define a HFO event as a subset of wave having significant high frequency component with low wave amplitude. HFO are detected from data recorded at a sampling rate of 12000 Hz for the entire duration of epileptogenesis which lasts anywhere from about 3–6 weeks. Statistical analysis on the HFO suggest that occurrence of HFO's occur primarily during the 12 hour dark cycle whereas the HFO's primarily seem to occur during the 12 hour day cycle in the control rat The video recording shows that the rat is primarily in active and exploratory state during the dark cycle. These observations suggest that HFO in epileptic rats are correlated with the state of arousal. Spatial correlation of HFOs in different regions of the brain is also investigated with cross-correlogram. Comparison of cross-correlogram of the post-stimulus HFO in the epileptic rat to the pre stimulus HFO (control) suggests modification in the circuitry in the hippocampus, evidence for which in in-vitro experiments were provided by [3].

Summary: Purpose: Phenylketonuria (PKU) is a disorder of phenylalanine (Phe) metabolism that frequently results in epilepsy if a low Phe diet was not implemented at birth. The mechanisms by which Phe affects the brain are poorly understood. Methods: Audiogenic seizures (AGS) were studied in female homozygous Pahenu2 BTBR (PKU) mice. Results: Adult PKU mice, 18–20 weeks of age, in contrast to wild-type and heterozygous counterparts, exhibited a full range of AGS. Younger PKU mice, 5–7 weeks of age, had higher serum Phe levels (2.22 ± 0.20 mM) in comparison with the adult animals (1.72 ± 0.05 mM) and were not susceptible to AGS. Among adult mice, animals susceptible to AGS had significantly lower serum Phe levels (1.62 ± 0.06 mM) in comparison with those resistant to AGS (1.86 ± 0.07 mM). Susceptibility to AGS tended to increase in the afternoon when serum Phe concentration decreased in comparison to evening and morning. Normalization of serum Phe level by instituting a low Phe diet generally prevented susceptibility to AGS within 12 h. Although return to a standard diet raised Phe levels to hyperphenylalaninemic within 12 h in animals treated with a low Phe diet for 2 weeks, more than 7 weeks were needed for a complete resumption of AGS. Conclusions: Transient decrease in Phe levels within hyperphenylalaninemic range may be a necessary condition for PKU-related seizures to occur. A low Phe diet prevents susceptibility to seizures, which can resume with the significant delay after termination of dietary treatment.

High Frequency Oscillations (HFO) in limbic epilepsy represent a marked difference between abnormal and normal brain activity. Faced with the difficult of visually detecting HFOs in large amounts of intracranial EEG data, it is necessary to develop an automated process. This paper presents Teager Energy as a method of finding HFOs. Teager energy is an ideal measure because unlike conventional energy it takes into account the frequency component of the signal as well as signal amplitude. This greatly aids in the dissection of HFOs out of the noise and other signals contained in the EEG. Therein, Teager energy analysis is able to detect high- frequency, low-amplitude components that conventional energy measurements would miss.

Epilepsy is a common neurological disorder that can have damaging effects in the brain including over 50% loss of neuronal activity in the hippocampal regions of the CA1 and CA3. The pre-ictal period was studied in an animal model of limbic epilepsy using Shannon entropy and correlation analysis. The primary aim was to uncover underlying relative changes in signals between the Dentate Gyrus and CA1 areas of the bilateral hippocampus. Preliminary entropy analysis results included dynamical changes between channels in the Dentate Gyrus and channels in the CA1 region at and around the time of the seizure. Epilepsy affects 3-5% of the population worldwide. Epilepsy is a neurological disorder characterized by recurrent and unprovoked seizures. An individual loses awareness when experiencing a complex partial seizure due to the spread of the seizure through both temporal lobes and subsequently impairing memory. (1) Of all cases, approximately 60% respond favorably to anti-epileptic drugs. (2) Regardless of age, sex or race, the harmful effects of limbic Epilepsy can be caused by past infections, vascular malformations, hamartomas and gliomas. Head trauma in the form of hemorrhaging or contusion in the brain often leads to the development of limbic Epilepsy after a number of months to years. This span of time is known as a latent period when cellular and network changes are thought to occur precipitating the onset of seizures. In epileptogenesis over 50% of the neurons in the hippocampal regions of the CA1 and CA3 are lost. Neuronal loss also occurs with the granule cells in the Dentate Gyrus; accompanying these changes is a loss of inhibitory neurons, excitatory neurons and excitatory axonal sprouting. (1) The Chronic Limbic Epilepsy rat model imitates human limbic epilepsy with the initial insult to the brain quiescent period and resultant seizures later in life. The manner in which these seizures develop is thought to be a result of structural changes in the brain such as the strengthening of excitatory networks, loss of inhibitory neurons or suppression of GABA receptors. (3) Since little is known about the time period over which the changes occur, it is proposed that detectable changes occur gradually within the brain over the latent period eventually causing the later hypersynchronous seizure activity. The link between the nature of the pre-ictal period and the electrical changes manifested in the brain are not well characterized. The abnormal mode of communication, a characteristic of seizures, is demonstrated by large- amplitude wave discharges occurring over a large hemisphere of the brain. The preictal period in an animal model of limbic epilepsy is studied using Shannon entropy measurements. The goal of this research is to characterize underlying changes in signals between the Dentate Gyrus and CA1 areas of the bilateral hippocampus.

Progressive preictal dynamical convergence and postictal divergence of dynamical EEG descriptors among brain regions has been reported in human temporal lobe epilepsy (TLE) and in a rodent model of TLE. There are also reports of anticonvulsant effects of high frequency stimulation of the hippocampus in humans. We postulate that this anticonvulsant effect is due to dynamical resetting by the electrical stimulation. The following study investigated the effects of acute hippocampal electrical stimulation on dynamical transitions in the brain of a spontaneously seizing animal model of TLE to test the hypothesis of divergence in dynamical values by electrical stimulation of the hippocampus.

Epilepsy research for the design of seizure detection/prediction neuroprosthetics has been faced with the search for electrophysiologic control parameters that can be used to infer the epileptic state of the animal and be leveraged at a later time to deliver neurotherapeutic feedback. The analysis presented here uses multi-microelectrode array technology to provide an electrophysiologic quantification of a hippocampal neural ensemble during the latent period of epileptogenesis. Through the use of signal processing system identification methodologies, we were able to assess the spatial and temporal interrelations of ensembles of hippocampal neurons and relate them to the evolution of the epileptic condition. High-field magnetic resonance (MR) imaging was used to determine the location of electrode placement and to evaluate hippocampal pyramidal cell structural damage. Long-term single unit activity analysis suggests that hippocampal neurons in both CA1-2 and dentate regions increase the number of occurrences and duration of their bursting activity after injury to the contra-lateral hippocampus. The trends inferred from both single neuron and ensemble analysis suggests that the evolution into epilepsy is not abrupt but modulates gradually from the time of injury.

Muscle surface capillary blood flow was measured in the biceps femoris and lateral head of the triceps brachii muscles in six horses before and during halothane anesthesia by using laser Doppler flowmetry. During 90 minutes of anesthesia, muscle surface capillary blood flow was reduced to 20% to 40% of preanesthetic values. Muscle surface capillary blood flow tended to be lower in dependent muscles than in nondependent muscles, and this disparity was greater in the forelimbs than in the hind limbs.

We determined the effects of ketamine HCI on cardiopulmonary function in 10 grey ratsnakes (Elaphe obsoleta), weighing 320 ? 150 g (mean ? SD). To establish normal values of cardiovascular response, we measured arterial blood pressure, carotid arterial blood flow, heart rates, breathing rates, and arterial blood gases in conscious snakes positioned both horizontally and in a 45* head-up tilt. Then we measured the same variables following intravascular administration of ketamine HCI (41 ? 6 mg/kg). Administration of ketamine produced significant tachycardia, hypertension, and decreases in breathing rates which were reflected in modest changes of arterial pH and respiratory gas pressures. Arterial oxygen saturation, however, exceeded 95% in both conscious and anesthetized snakes. Administration of ketamine produced nearly twofold increases in systolic, diastolic, mean, and pulse systemic arterial pressures of resting snakes in horizontal position. In response to head-up tilt, central arterial pressures decreased in anesthetized snakes but did not fall below levels that were regulated by reflexogenic increases in conscious snakes. Thus, administration of ketamine HCI to snakes produced significant hypertension but did not seriously compromise cardiovascular performance in response to gravitational stress.

Interstitial pressure and pH in the dependent biceps femoris muscle were measured in anesthetized, laterally recumbent horses. The mean (+/- standard deviation) interstitial pressure in 10 horses was 19.70 +/- 0.15 mmHg in the 30 to 180 minute interval after induction of anesthesia. Pressures of this order have been associated with reduction in muscle perfusion. Mean (+/- standard deviation) interstitial pH in six horses decreased from 7.07 +/- 0.30 to 6.73 +/- 0.21 between 45 and 150 minutes of anesthesia. These results indicated the presence of circulatory compromise to intracompartmental structures.