The Journal of Neurophysiology Vol. 79 No. 1 January 1998, pp. 95-105
Copyright ©1998 The American Physiological Society

Axon Conduction and Survival in CNS White Matter During Energy Deprivation: A Developmental Study

Robert Fern¹, Peter Davis², Stephen G. Waxman^{2, 3}, and Bruce R. Ransom¹

¹ Department of Neurology, University of Washington, Seattle, Washington 98195; ² Department of Neurology, Yale University School of Medicine, New Haven 06510; and ³ Neuroscience Research Center, Department of Veterans Affairs Medical Center, West Haven, Connecticut 16516

Fern, Robert, Peter Davis, Stephen G. Waxman, and Bruce R. Ransom. Axon conduction and survival in CNS white matter during energy deprivation: a developmental study. J. Neurophysiol. 79: 95-105, 1998. We investigated the postnatal development of axon sensitivity to the withdrawal of oxygen, glucose, or the combined withdrawal of oxygen + glucose in the isolated rat optic nerve (a CNS white matter tract). Removal of either oxygen or glucose for 60 min resulted in irreversible injury in optic nerves from adult rats, assessed by loss of the evoked compound action potential (CAP). Optic nerves at ages <P10 showed no permanent loss of function. CAP sensitivity to the withdrawal of oxygen or glucose emerged during a critical period in development between postnatal days 10-20 (P10-P20). The CAP was unchanged in adult optic nerve for 45 min after the withdrawal of glucose, demonstrating the presence of a significant energy reserve. Periods of glucose withdrawal >45 min caused the selective loss of late CAP components; this was not seen with oxygen deprivation. The amplitude of the early component recovered to 94.8% of control after 60 min of glucose withdrawal, although total CAP area recovered to only 42.3%. Combined oxygen + glucose withdrawal for 60 min produced a greater degree of permanent CAP loss than 60 min of glucose or oxygen withdrawal individually in optic nerves from rats older than P4. Younger than P4 optic nerves showed no permanent loss of function from 60 min of combined oxygen + glucose withdrawal. Unexpectedly, optic nerves from P21-P49 rats recovered significantly less after all three conditions than adult opticnerves (>P50). It is probable that this period of final myelination corresponds to a time of heightened metabolic activity in white matter. The tolerance of CNS white matter to energy deprivation can be categorized into four stages that are correlated with specific developmental features: premyelination (P0-P4), highly tolerant to anoxia, aglycemia and combined anoxia/aglycemia; early myelination (P5-P20), partially tolerant of anoxia and aglycemia but not to combined anoxia/aglycemia; late myelination (P21-P49), very low tolerance of anoxia, aglycemia and combined anoxia/aglycemia; and mature (>P50), low tolerance of anoxia, aglycemia and combined anoxia/aglycemia. The relative resistance of optic nerve function to glucose withdrawal in the presence of oxygen, compared with glucose withdrawal in the absence of oxygen, is presumably due to the presence of oxygen-dependent energy reserves such as astrocytic glycogen, amino acids. and phospholipids.

This article has been cited by other articles:

				J. J. P. Alix, A. C. Dolphin, and R. Fern Vesicular apparatus, including functional calcium channels, are present in developing rodent optic nerve axons and are required for normal node of Ranvier formation J. Physiol., September 1, 2008; 586(17): 4069 - 4089. [Abstract] [Full Text] [PDF]

				W. J. McCarran and M. P. Goldberg White Matter Axon Vulnerability to AMPA/Kainate Receptor-Mediated Ischemic Injury Is Developmentally Regulated J. Neurosci., April 11, 2007; 27(15): 4220 - 4229. [Abstract] [Full Text] [PDF]

				B. Weber, V. Treyer, N. Oberholzer, T. Jaermann, P. Boesiger, P. Brugger, M. Regard, A. Buck, S. Savazzi, and C. A. Marzi Attention and Interhemispheric Transfer: A Behavioral and fMRI Study J. Cogn. Neurosci., January 1, 2005; 17(1): 113 - 123. [Abstract] [Full Text] [PDF]

				M. F. Cano-Abad, M. Villarroya, A. G. Garcia, N. H. Gabilan, and M. G. Lopez Calcium Entry through L-type Calcium Channels Causes Mitochondrial Disruption and Chromaffin Cell Death J. Biol. Chem., October 19, 2001; 276(43): 39695 - 39704. [Abstract] [Full Text] [PDF]

				S. B. Tekkok and M. P. Goldberg AMPA/Kainate Receptor Activation Mediates Hypoxic Oligodendrocyte Death and Axonal Injury in Cerebral White Matter J. Neurosci., June 15, 2001; 21(12): 4237 - 4248. [Abstract] [Full Text] [PDF]

				R. Wender, A. M. Brown, R. Fern, R. A. Swanson, K. Farrell, and B. R. Ransom Astrocytic Glycogen Influences Axon Function and Survival during Glucose Deprivation in Central White Matter J. Neurosci., September 15, 2000; 20(18): 6804 - 6810. [Abstract] [Full Text] [PDF]

				R. Fern Intracellular Calcium and Cell Death during Ischemia in Neonatal Rat White Matter Astrocytes In Situ J. Neurosci., September 15, 1998; 18(18): 7232 - 7243. [Abstract] [Full Text] [PDF]