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Bruce R Ransom

Publications and source records attributed to Bruce R Ransom.

20 records · Page 2Linked to original sources
PubMed2002

Neuroprotective effects of increased extracellular Ca(2+) during aglycemia in white matter.

We investigated the effects of extracellular [Ca(2+)] ([Ca(2+)](o)) on aglycemia-induced dysfunction and injury in adult rat optic nerves. Compound action potentials (CAPs) from adult rat optic nerve were recorded in vitro, and the area under the CAP was used to monitor nerve function before and after 1 h periods of aglycemia. In control artificial cerebrospinal fluid (ACSF) containing 2 mM Ca(2+), CAP function fell after 29.9 +/- 1.5 (SE) min and recovered to 48.8 +/- 3.9% following aglycemia. Reducing bath [Ca(2+)] during aglycemia progressively improved recovery. For example, in Ca(2+)-free ACSF, the CAP recovered to 99.1 +/- 3.8%. Paradoxically, increasing bath [Ca(2+)] also improved recovery from aglycemia. In 5 or 10 mM bath [Ca(2+)], CAP recovered to 78.8 +/- 9.2 or 91.6 +/- 5.2%, respectively. The latency to CAP failure during aglycemia increased as a function of bath [Ca(2+)] from 0 to 10 mM. Increasing bath [Mg(2+)] from 2 to 5 or 10 mM, with bath [Ca(2+)] held at 2 mM, increased latency to CAP failure with aglycemia and improved recovery from this insult. [Ca(2+)](o) recorded with calcium-sensitive microelectrodes in control ACSF, dropped reversibly during aglycemia from 1.54 +/- 0.03 to 0.45 +/- 0.04 mM. In the presence of higher ambient levels of bath [Ca(2+)] (i.e., 5 or 10 mM), the aglycemia-induced decrease in [Ca(2+)](o) declined, indicating that less Ca(2+) left the extracellular space to enter an intracellular compartment. These results indicate that the role of [Ca(2+)], and divalent cations in general, during aglycemia is complex. While extracellular Ca(2+) was required for irreversible aglycemic injury to occur, higher levels of [Ca(2+)] or [Mg(2+)] increased the latency to CAP failure and improved the extent of recovery, apparently by limiting Ca(2+) influx. These effects are theorized to be mediated by divalent cation screening.

Action Potentials↗
PubMedDate not supplied

Astrocyte glycogen metabolism is required for neural activity during aglycemia or intense stimulation in mouse white matter.

We tested the hypothesis that inhibiting glycogen degradation accelerates compound action potential (CAP) failure in mouse optic nerve (MON) during aglycemia or high-intensity stimulation. Axon function was assessed as the evoked CAP, and glycogen content was measured biochemically. Isofagomine, a novel inhibitor of central nervous system (CNS) glycogen phosphorylase, significantly increased glycogen content under normoglycemic conditions. When MONs were bathed in artificial cerebrospinal fluid (aCSF) containing 10 mM glucose, the CAP failed 16 min after exposure to glucose-free aCSF. MONs bathed in aCSF plus isofagomine displayed accelerated CAP failure on glucose removal. Similar results were obtained in MONs bathed in 30 mM glucose, which increased baseline glycogen concentration. The ability of isofagomine to increase glycogen content thus was not translated into delayed CAP failure. This is likely due to the inability of the tissue to metabolize glycogen in the presence of isofagomine, highlighting the importance of glycogen in sustaining neural function during aglycemia. The hypothesis that glycogen breakdown supports intense neural activity was tested by blocking glycogen breakdown during periods of high-frequency stimulation. The CAP area declined more rapidly when glycogen metabolism was inhibited by isofagomine, explicitly showing an important physiological role for glycogen metabolism during neural activity.

Action Potentials↗