Biomedical subjects

H S Lukatch

Publications and source records attributed to H S Lukatch.

6 recordsLinked to original sources

PubMed2000

Hypoglycemic and hypoxic modulation of cortical micro-EEG activity in rat brain slices.

OBJECTIVE: Electroencephalogram (EEG) recordings exhibit stereotypic alterations during transient ischemia in mammals. One disadvantage of using in vitro models for ischemia studies is the lack of a sensitive electrophysiological measure for the degree of ischemic damage to a large population of neurons. The present study examined effects of hypoglycemia, hypoxia or both on an in vitro micro-EEG model, to determine whether this model provides a sensitive measure. METHODS: Theta frequency (4-8 Hz) micro-EEG oscillations were evoked in rat neocortical brain slices using the cholinergic agonist carbachol (100 microM) and the GABA(A) antagonist bicuculline (10 microM). Extracellular field micro-EEG signals and whole cell patch clamp recordings were used to monitor electrical activity. RESULTS: Upon removal of oxygen and/or glucose, theta oscillation amplitudes progressively declined to isoelectric levels. Low frequency delta oscillations (0.5-3.0 Hz) and burst suppression discharges were prominent during hypoglycemic episodes and upon recovery. Time to onset of isoelectric activity was faster in slices deprived of both glucose and oxygen (7.0 +/- 1.8 min) and oxygen alone (5.0 +/- 1.5 min) compared to hypoglycemia alone (25.6 +/- 3.8 min, P < 0.01, ANOVA). Hypoxia and hypoglycemia-induced isoelectric activity occurred prior to significant population spike depression from control levels (87.7 +/- 16.9% control amplitude, P > 0.35 (t test compared with control) for hypoglycemia; 93.6 +/- 27.0%, P > 0.72 for hypoxia). Spreading depression (SD) was observed in 11/12 (91.7%) slices deprived of both sugar and oxygen, but not in hypoxic (0/4) or hypoglycemic (0/5) slices. In all cases, SD occurred later than isoelectric activity. Theta oscillations recovered within 10 min in 12/13 (92.3%) slices that did not undergo SD, but slices that underwent SD failed to recover theta activity (0/4), though all (4/4) at least partially recovered the population spike (>40%). CONCLUSIONS: These results suggest that synchronized micro-EEG activity may be a useful and sensitive indicator of early-onset and possibly reversible ischemic damage.

Animals↗

PubMed1997

Voltage-clamp analysis of halothane effects on GABA(A fast) and GABA(A slow) inhibitory currents.

Voltage-clamped GABA(A fast) and GABA(A slow) inhibitory postsynaptic currents (IPSCs) were selectively elicited in hippocampal area CA1 pyramidal neurons. Clinically relevant concentrations of halothane (1.2 vol.%) prolonged both GABA(A fast) and GABA(A slow) IPSC decay times approximately 2.5 fold, while having little to no effect on current amplitudes or rise times. Current-voltage analysis revealed that IPSC reversal potentials (-70 to -75 mV) remained constant in the presence of halothane. Under control conditions, GABA(A slow) IPSC decay times increased linearly with membrane depolarization, and this IPSC decay time voltage dependence was not significantly altered by halothane. These results confirm the existence of separable GABA(A fast) and GABA(A slow) IPSCs in hippocampus, and further elucidate the effects of halothane on these currents.

Anesthetics, General↗

PubMed1997

G-force induced alterations in rat EEG activity: a quantitative analysis.

A major physical limitation affecting pilots is G-force (+Gz, head-to-foot inertial load) induced loss of consciousness. Previous studies have shown that +Gz produces qualitatively similar effects on human and rat EEG activity. The present study sought to quantitatively correlate changes in rat EEG activity with increasing +Gz levels. A frontal-parietal differential electrode recorded rat EEG data during +Gz exposures (30 s) ranging from +0.5 to +25.0 Gz. Acceleration levels < or = +10 Gz had little effect on EEG activity. Acceleration levels of +15 to +20 Gz were associated with increased EEG slowing, depression and sharp waves. Acceleration levels > or = +17.5 Gz evoked burst suppression followed by isoelectric activity. Times to first onset of delta, depressed, and isoelectric EEG activity were approximately 12, 14 and 18 s, respectively. Acceleration effects on delta (1-4 Hz), theta (5-8 Hz), alpha (9-12 Hz), beta (13-30 Hz) and total (1-30 Hz) EEG powers were examined using Fourier transform analysis. EEG measures with the most predictive value at the following post-acceleration onset times (PAOT) were as follows (in s); increasing theta power: PAOT 0-2, decreasing delta power: PAOT 3-9, and decreasing beta power: PAOT > or = 12. This study provides a quantitative description of +Gz-induced alterations in EEG magnitude, time course and spectral content. Additionally, several EEG measures were identified which correlated with acceleration level at specific post-acceleration onset times.

Alpha Rhythm↗

PubMed1997

Physiology, pharmacology, and topography of cholinergic neocortical oscillations in vitro.

Rat neocortical brain slices generated rhythmic extracellular field [microelectroencephalogram (micro-EEG)] oscillations at theta frequencies (3-12 Hz) when exposed to pharmacological conditions that mimicked endogenous ascending cholinergic and GABAergic inputs. Use of the specific receptor agonist and antagonist carbachol and bicuculline revealed that simultaneous muscarinic receptor activation and gamma-aminobutyric acid-A (GABA(A))-mediated disinhibition were necessary to elicit neocortical oscillations. Rhythmic activity was independent of GABA(B) receptor activation, but required intact glutamatergic transmission, evidenced by blockade or disruption of oscillations by 6-cyano-7-nitroquinoxaline-2,3-dione and (+/-)-2-amino-5-phosphonovaleric acid, respectively. Multisite mapping studies showed that oscillations were localized to areas 29d and 18b (Oc2MM) and parts of areas 18a and 17. Peak oscillation amplitudes occurred in layer 2/3, and phase reversals were observed in layers 1 and 5. Current source density analysis revealed large-amplitude current sinks and sources in layers 2/3 and 5, respectively. An initial shift in peak inward current density from layer 1 to layer 2/3 indicated that two processes underlie an initial depolarization followed by oscillatory activity. Laminar transections localized oscillation-generating circuitry to superficial cortical layers and sharp-spike-generating circuitry to deep cortical layers. Whole cell recordings identified three distinct cell types based on response properties during rhythmic micro-EEG activity: oscillation-ON (theta-ON) and -OFF (theta-OFF) neurons, and transiently depolarizing glial cells. Theta-ON neurons displayed membrane potential oscillations that increased in amplitude with hyperpolarization (from -30 to -90 mV). This, taken together with a glutamate antagonist-induced depression of rhythmic micro-EEG activity, indicated that cholinergically driven neocortical oscillations require excitatory synaptic transmission. We conclude that under the appropriate pharmacological conditions, neocortical brain slices were capable of producing localized theta frequency oscillations. Experiments examining oscillation physiology, pharmacology, and topography demonstrated that neocortical brain slice oscillations share many similarities with the in vivo and in vitro theta EEG activity recorded in other brain regions.

Animals↗

PubMed1996

Synaptic mechanisms of thiopental-induced alterations in synchronized cortical activity.

BACKGROUND: Anesthetic depth after barbiturate administration has been correlated with distinct electroencephalogram (EEG) patterns. The current study used a rat neocortical brain slice micro-EEG preparation to investigate synaptic mechanisms underlying thiopental-induced transitions in synchronized neuronal activity. METHODS: Concentration-dependent cellular actions of thiopental were investigated in brain slices using specific pharmacologic probes, whole cell patch clamps, and extracellular field recordings. Theta-Like micro-EEG oscillations were elicited in neocortical slices by mimicking subcortical cholinergic and gamma-aminobutyric acid (GABA) afferent input with carbachol (100 microM), a cholinergic agonist, and bicuculline (10 microM) a GABAA antagonist. RESULTS: In the presence of 20 microM thiopental, micro-EEG slowing from theta (7.3 +/- 0.9 Hz, mean +/- SD, n = 19) to delta frequencies (2.5 +/- 0.5 Hz, n = 11) was associated with a threefold prolongation of inhibitory currents. Burst suppression activity occurred at 50 microM thiopental, and appeared to result from direct activation of GABAA-gated chloride currents, observed with voltage clamp recordings, and mimicked with a direct acting GABAA agonist, muscimol (1 microM). Isoelectric activity occurred at 100 microM thiopental, and likely resulted from reduced glutamatergic transmission, evidenced by depressed excitatory postsynaptic potentials. Glutamatergic excitation was required for burst suppression activity, because glutamate receptor antagonists blocked thiopental-induced bursts; forcing a transition to isoelectric activity. CONCLUSIONS: Thiopental produced a continuum of EEG-like states in brain slices similar to those observed in vivo. The progression of thiopental-induced effects appear to have resulted from specific cellular actions that were recruited in a concentration-dependent manner. Progressive enhancement of synaptic inhibition followed by depression of excitatory transmission led to micro-EEG frequency slowing, burst suppression, and isoelectric activity.

Anesthetics, Intravenous↗

PubMed1995

Diltiazem spares corneal A delta mechano and C fiber cold receptors and preserves epithelial wound healing.

Recent interest in the corneal analgesic properties of diltiazem prompted the present study examining concentration-dependent effects of this calcium channel blocker on C fiber cold receptors and A delta mechanoreceptors. Both afferent fiber types mediate an eye blink reflex, important for protecting the corneal surface. The effects of neuroactive concentrations of diltiazem on corneal would healing were also studied. An in vitro rabbit cornea preparation was used for both electrophysiological recording and wound healing, allowing precise concentration-response analysis. Diltiazem produced a concentration-dependent depression of cold fiber discharge activity (10 to 250 microM), but did not affect mechanoreceptor afferents. In addition, the broad spectrum Ca2+ channel blockers, Ni2+ and Cd2+, did not cause a significant reduction in A delta mechano or C fiber discharge activity. Diltiazem had no effect on corneal epithelial wound healing to a concentration of 50 microM. This is important if diltiazem is to be used for therapeutic control of pain following corneal injury or surgery, because sparing of the eye blink reflexes and wound healing are desirable properties for a corneal analgesic.

Animals↗