Painted Turtle Cortex is Resistant to anin VitroMimic of the Ischemic Mammalian Penumbra

Abstract

Anoxia or ischemia causes hyperexcitability and cell death in mammalian neurons. Conversely, in painted turtle brain anoxia increases c-amino butyric acid (GABA)ergic suppression of spontaneous electrical activity, and cell death is prevented. To examine ischemia tolerance in turtle neurons, we treated cortical sheets with an in vitro mimic of the penumbral region of strokeafflicted mammalian brain (ischemic solution, IS). We found that during IS perfusion, neuronal membrane potential (V m ) and the GABA A receptor reversal potential depolarized to a similar steady state (À92 ± 2 to À28 ± 3 mV, and À75 ± 1 to À35 ± 3 mV, respectively), and whole-cell conductance (G w ) increased > 3-fold (from 4 ± 0.2 to 15 ± 1 nS). These neurons were electrically quiet and changes reversed after reperfusion. GABA receptor antagonism prevented the IS-mediated increase in G w and neurons exhibited enhanced electrical excitability and rapid and irreversible rundown of V m during reperfusion. These results suggest that inhibitory GABAergic mechanisms also suppress electrical activity in ischemic cortex. Indeed, after 4 hours of IS treatment neurons did not exhibit any apparent damage; while at 24 hours, only early indicators of apoptosis were present. We conclude that anoxia-tolerant turtle neurons are tolerant of exposure to a mammalian ischemic penumbral mimic solution.

Decreases in mitochondrial reactive oxygen species initiate GABAA receptor‐mediated electrical suppression in anoxia‐tolerant turtle neurons

“…As a result, the brain of this species is remarkably tolerant of complete anoxia and also of global or focal ischaemia and high K + insults (Pamenter et al . ). To reduce cellular energy consumption during anoxia, AP firing frequency decreases due to a neuroprotective strategy termed spike arrest (SA) (Perez‐Pinzon et al .…”

Epigenetics and the Environment: In Search of the “Toleroasome” Vital to Execution of Ischemic Preconditioning

“…Elegant studies from a number of groups, particularly those of Frank Sharp [40], Jeffrey Gidday [12], John Zhang [54, 55], Gabriel Haddad [29], Sylvain Dore [52], and Mary Stenzel-Poore and Roger Simon [44], have shown that the ischemic-tolerant brain is characterized by both repression and activation of gene expression. These studies have been complemented by an understanding of the “proteomic signature” that is associated with such induction and repression [43].…”

Phosphorylation of the mitochondrial ATP-sensitive potassium channel occurs independently of PKCε in turtle brain

“…It is understood that PKCε plays an important role in IPC in mammalian neurons, as demonstrated by its membrane translocation during IPC and its importance in limiting infarct damage during ischemia and reperfusion (Kawamura et al, 1998). One could make the argument that the western painted turtle and other anoxia-tolerant organisms are chronically pre-conditioned for periods of anoxia and ischemia, as these organisms can tolerate ischemic episodes without shorter, sub-lethal preceding exposures (Pamenter et al, 2012). By this argument, it would be logical to presume that factors critical for IPC in anoxia-sensitive organisms would be highly expressed at rest in anoxia-tolerant organisms.…”