Acute Cellular Alterations in the Hippocampus After Status Epilepticus

The critical, fundamental mechanisms that determine the emergence of status epilepticus from a single seizure and the prolonged duration of status epilepticus are uncertain. However, several general concepts of the pathophysiology of status epilepticus have emerged: (a) the hippocampus is consistently activated during status epilepticus; (b) loss of GABA-mediated inhibitory synaptic transmission in the hippocampus is critical for emergence of status epilepticus; and, finally (c) glutamatergic excitatory synaptic transmission is important in sustaining status epilepticus. This review focuses on the alteration of GABAergic inhibition in the hippocampus that occurs during the prolonged seizures of status epilepticus. If reduction in GABAergic inhibition leads to development of status epilepticus, enhancement of GABAergic inhibition would be expected to interrupt status epilepticus. Benzodiazepines and barbiturates are both used in the treatment of status epilepticus and both drugs enhance GABA A receptor-mediated inhibition. However, patients often become refractory to benzodiazepines when seizures are prolonged, and barbiturates are often then used for these refractory cases of status epilepticus. Recent evidence suggests the presence of multiple GABA A receptor isoforms in the hippocampus with different sensitivity to benzodiazepines but similar sensitivity to barbiturates, thus explaining why the two drug classes might have different clinical effects. In addition, rapid functional plasticity of GABA A receptors has been demonstrated to occur during status epilepticus in rats. During status epilepticus, there was a substantial reduction of diazepam potency for termination of the seizures. The loss of sensitivity of the animals to diazepam during status epilepticus was accompanied by an alteration in the functional properties of hippocampal dentate granule cell GABA A receptors. Dentate granule cell GABA A receptor currents from rats undergoing status epilepticus had reduced sensitivity to diazepam and zinc but normal sensitivity to GABA and pentobarbital. Therefore, the prolonged seizures of status epilepticus rapidly altered the functional properties of hippocampal dentate granule cell GABA A receptors, possibly explaining why benzodiazepines and barbiturates may not be equally effective during treatment of the prolonged seizures of status epilepticus. A comprehensive understanding of the cellular and molecular events leading to the development, maintenance, and cytotoxicity of status epilepticus should permit development of more effective treatment strategies and reduction in the mortality and morbidity of status epilepticus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65664/1/j.1528-1157.1999.tb00873.x.pd

Hearing Loss Prevents the Maturation of GABAergic Transmission in the Auditory Cortex

Inhibitory neurotransmission is a critical determinant of neuronal network gain and dynamic range, suggesting that network properties are shaped by activity during development. A previous study demonstrated that sensorineural hearing loss (SNHL) in gerbils leads to smaller inhibitory potentials in L2/3 pyramidal neurons in the thalamorecipient auditory cortex, ACx. Here, we explored the mechanisms that account for proper maturation of γ-amino butyric acid (GABA)ergic transmission. SNHL was induced at postnatal day (P) 10, and whole-cell voltage-clamp recordings were obtained from layer 2/3 pyramidal neurons in thalamocortical slices at P16–19. SNHL led to an increase in the frequency of GABAzine-sensitive (antagonist) spontaneous (s) and miniature (m) inhibitory postsynaptic currents (IPSCs), accompanied by diminished amplitudes and longer durations. Consistent with this, the amplitudes of minimum-evoked IPSCs were also reduced while their durations were longer. The α1- and β2/3 subunit–specific agonists zolpidem and loreclezole increased control but not SNHL sIPSC durations. To test whether SNHL affected the maturation of GABAergic transmission, sIPSCs were recorded at P10. These sIPSCs resembled the long SNHL sIPSCs. Furthermore, zolpidem and loreclezole were ineffective in increasing their durations. Together, these data strongly suggest that the presynaptic release properties and expression of key postsynaptic GABAA receptor subunits are coregulated by hearing

Interneuron- and GABAA receptor-specific inhibitory synaptic plasticity in cerebellar purkinje cells

Inhibitory synaptic plasticity is important for shaping both neuronal excitability and network activity. Here we investigate the input and GABA(A) receptor subunit specificity of inhibitory synaptic plasticity by studying cerebellar interneuron-Purkinje cell (PC) synapses. Depolarizing PCs initiated a long-lasting increase in GABA-mediated synaptic currents. By stimulating individual interneurons, this plasticity was observed at somatodendritic basket cell synapses, but not at distal dendritic stellate cell synapses. Basket cell synapses predominantly express β2-subunit-containing GABA(A) receptors; deletion of the β2-subunit ablates this plasticity, demonstrating its reliance on GABA(A) receptor subunit composition. The increase in synaptic currents is dependent upon an increase in newly synthesized cell surface synaptic GABA(A) receptors and is abolished by preventing CaMKII phosphorylation of GABA(A) receptors. Our results reveal a novel GABA(A) receptor subunit- and input-specific form of inhibitory synaptic plasticity that regulates the temporal firing pattern of the principal output cells of the cerebellum

A Classification Regression Tree Analysis to Reduce Balance Impairments and Falls in the Older population: Impact on Resource Utilization and Clinical Decision-Making in USA Rehabilitation Service Delivery

Background/Purpose: Over 1/3 of adults over age 65 experiences at least one fall each year. This pilot report uses a classification regression tree analysis (CART) to model the outcomes for balance/risk of falls from the Gentiva® Safe Strides® Program (SSP). Methods/Outcomes: SSP is a home-based balance/fall prevention program designed to treat root causes of a patien

Improvements in balance in older adults engaged in a specialized home care falls prevention program

Background and Purpose: To determine if persons older than 65 years receiving a combination of physical therapy, occupational therapy, speech, or nursing interventions in their home demonstrated changes in gait/balance function after an episode of home care services. Methods: Charts from 11 667 persons who were at risk for falling and who were participating in an exercise program in the home were included. Study design: Data were retrieved from the Outcome and Assessment Information Set, Version B, and the computerized database of physical therapist-collected outcome data. Recorded physical therapist-data may have included a neuropathic pain rating, the Berg Balance Scale (BBS), the Performance Oriented Measurement Assessment (POMA), the Dynamic Gait Index (DGI), and the modifi ed Clinical Test of Sensory Integration and Balance (mCTSIB). Data analysis: Data were extracted by an honest broker and were analyzed. Mean (SD) change in each performance test and the percentage of participants in the total sample and in the 9 age/health condition strata that exceeded the minimum detectable change (MDC) for each gait/balance measure were described. The value of MDC95 describes the amount of true change in participant status beyond measurement error with 95% certainty. Results: The gait/balance measures demonstrated MDCs ranging between 68% and 91% for the study sample. Mean (SD) of improvement on the BBS was 12 (8) points, with 88% of all participants exceeding the BBS MDC95 value of 5 points. Mean (SD) of improvement in gait/balance performance as measured by the POMA was 8 (4) points, with 91% of all participants exceeding the POMA MDC95 value of 3 points. Among all patients, mean (SD) of improvement on the DGI was 7 (4) points with 91% of all participants exceeding the DGI MDC95 value of 2 points by discharge. At admission, the median number of mCTSIB conditions that could be completed was 1 and the median number of completed conditions on the mCTSIB increased to 3 at discharge, with 81% of all participants demonstrating improvement. Conclusion: On the basis of established criteria, participants seemed to make clinically meaningful gains after the home care episode of care. Copyright © 2013 The Section on Geriatrics of the American Physical Therapy Association