Temporal profile of aminergic neurotransmitter release in striatal dialysates in rats with post-ischemic seizures

Abstract

The temporal profiles of aminergic neurotransmitter levels and of their acid metabolites after transient global cerebral ischemia in awake rats with and without subsequent seizures were compared using a microdialysis approach. In seizure animals, the post-ischemic levels of dopamine and serotonin were higher than the levels observed in the non-seizure controls. Inversely, the levels of the three neurotransmitter metabolites increased rapidly in the controls but not in seizure animals, where they remained at the low levels observed during and immediately after ischemia. This particular pattern is similar to that observed in rats submitted to prolonged ischemia or pretreated with monoamine oxidase inhibitors. In the seizure animals, neurotransmitter metabolites remained at low levels, as if the hypoxia had continued after the period of ischemia, inhibiting monoamine oxidase activity and, perhaps, neurotransmitter recapture.

Neurotransmitters and neuromodulators controlling the hypoxic respiratory response in anaesthetized cats

“…However, it appears that depression of neuronal excitability and synaptic interactions between bulbar respiratory neurones play an important role (Richter et al 1991). Mechanisms underlying such disturbances may involve: (i) a generalized release and local accumulation of inhibitory neurotransmitters (Neubauer et al 1990;Haddad & Jiang, 1992;Young et al 1992;Katoh et al 1997) andÏor neuromodulators such as adenosine, catecholamines, serotonin and opioids (Runold et al 1989;Neubauer et al 1990;Moss et al 1993;Bentue-Ferrer et al 1994;Yan et al 1995); (ii) activation of ATP-sensitive potassium (KATP) channels of respiratory neurones due to a decrease in intracellular ATP levels (Jiang & Haddad, 1991;Haddad & Jiang, 1993;Pierrefiche et al 1996); and (iii) accumulation of metabolic byproducts such as adenosine (Schmidt et al 1995), which augment KATP channel currents in postsynaptic neurones (Mironov et al 1998) and depress the otherwise increased Ca¥ influx in cell bodies and axon terminals and consequently release of neurotransmitters. A previous intracellular investigation (Richter et al 1991) showed that, during hypoxia, there is an orderly temporal sequence of membrane potential changes in medullary respiratory neurones.…”

Rodent Models of Global Cerebral Ischemia

“…In addition, there is substantial literature on ischemia‐induced increases in extracellular neurotransmitter levels after 4‐VO. For example, large increases in extracellular dopamine and serotonin (Phebus and Clemens, ; Bentué‐Ferrer et al, ) and glutamate and aspartate (Benveniste et al, ) have been reported after ischemia in this model.…”

“…Although the rat 4-VO and gerbil BCAO models are both models of global cerebral ischemia, many compounds (e.g., NMDA antagonists) that provide neuroprotection in the gerbil model provide minimal or no neuroprotection in the rat. The 4-VO model is surgically more challenging, and some rats exhibit seizures after the initial electrocoagulation of the vertebral arteries (Bentué-Ferrer et al, 1994). Another disadvantage of this model is unsuccessful outcome in up to 25% of rats.…”

Strain Variability, Injury Distribution, and Seizure Onset in a Mouse Model of Stroke in the Immature Brain

“…Seizures induced by global hypoxia, global ischemia, or hypoxic-ischemic injury have been reported in adult and immature rats [47][48][49] . Studies examining interactions between seizures and hypoxic-ischemic brain injury in developing rats have produced confl icting results.…”