Elsevier

Neuroscience

Volume 115, Issue 3, 9 December 2002, Pages 917-929
Neuroscience

Vulnerability of the thalamic somatosensory pathway after prolonged global hypoxic–ischemic injury

https://doi.org/10.1016/S0306-4522(02)00369-XGet rights and content

Abstract

The aim of this study was to test the hypothesis that under prolonged global ischemic injury, the somatosensory thalamus and the cortex would manifest differential susceptibility leading to varying degrees of thalamo-cortical dissociation. The thalamic electrical responses displayed increasing suppression with longer durations of ischemia leading to a significant thalamo-cortical electrical dissociation. The data also point to a selective vulnerability of the network oscillations involving the thalamic relay and reticular thalamic neurons.

An adult rat model of asphyxial cardiac arrest involving three cohorts with 3 min (G1, n=5), 5 min (G2, n=5) and 7 min (G3, n=5) of asphyxia respectively was used. The cortical evoked response, as quantified by the peak amplitude at 20 ms in the cortical evoked potential, recovers to more than 60% of baseline in all the cases. The multi-unit responses to the somatosensory stimuli recorded from the thalamic ventral posterior lateral (VPL) nuclei consists typically of three components: (1) the ON response (<30 ms after stimulus), (2) the OFF response (period of inhibition, from 30 ms to 100 ms after stimulus) and (3) rhythmic spindles (beyond 100 ms after stimulus). Asphyxia has a significant effect on the VPL ON response at 30 min (P<0.025), 60 min (P<0.05) and 90 min (P<0.05) after asphyxia. Only animals in G3 show a significant suppression (P<0.05) of the VPL ON response when compared to the sham group at 30 min, 60 min and 90 min after asphyxia. There was no significant reduction in somatosensory cortical N20 (negative peak in the cortical response at 20 ms after stimulus) amplitude in any of the three groups with asphyxia indicating a thalamo-cortical dissociation in G3. Further, rhythmic spindle oscillations in the thalamic VPL nuclei that normally accompany the ON response recover either slowly after the recovery of ON response (in the case of G1 and G2) or do not recover at all (in the case of G3).

We conclude that there is strong evidence for selective vulnerability of thalamic relay neurons and its network interactions with the inhibitory interneurons in the somatosensory pathway leading to a thalamo-cortical dissociation after prolonged durations of global ischemia.

Section snippets

Experimental procedures

All procedures were carried out with the approval of the Institute Animal Care and Use Committee of Johns Hopkins University, Baltimore, MD, USA. The experiments were carried out in accordance with the National Institute of Health (NIH) guide for the care and use of laboratory animals (NIH publications No. 80-23) revised 1978. All efforts were made to minimize animal suffering and to use only the number of animals necessary to produce reliable scientific data, and to utilize alternatives to in

Multi-unit activity in thalamus

The number of VPL neurons recorded from each animal varied between one and six. The total number of VPL neurons recorded were 17 in G1 and 18 each in G2 and G3. The number and types of units recorded at the end of each experiment were generally different from those recorded during baseline due to changes in the shape of action potentials during the experiment.

The multi-unit responses to the somatosensory stimuli recorded from the VPL consisted typically of three components: the ON response (<30

Discussions

The overall goal of this study was to investigate the acute effects of graded ischemic injury on electrophysiological indicators of function in the cortical and thalamic structures along the somatosensory pathway. We have specifically tested for differential vulnerability between the electrical indicators of somatosensory cortical and thalamic functions. We have also used the direct electrical responses of the thalamic relay neurons to somatosensory stimulus as well as the accompanying spindle

Acknowledgements

Research supported by a Grant NS24282 from the NIH. R.G. was supported by the David S. Dana Research prize.

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