title: Vulnerability of the thalamic somatosensory pathway after prolonged global hypoxic-ischemic injury.
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.
authors.affiliation: Department of Bioengineering, PO Box 879709, College of Engineering and Applied Sciences, Arizona State University, Tempe, AZ 85287-9709, USA. jit@asu.edu
authors.forename: J
authors.initials: J
authors.lastname: Muthuswamy
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: M C
authors.initials: MC
authors.lastname: Ding
authors.forename: R
authors.initials: R
authors.lastname: Geocadin
authors.forename: D F
authors.initials: DF
authors.lastname: Hanley
authors.forename: N V
authors.initials: NV
authors.lastname: Thakor
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001683:Biological Clocks / Q000502:physiology; D002470:Cell Survival / Q000502:physiology*; D004195:Disease Models, Animal; D004569:Electroencephalography; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D006324:Heart Arrest, Induced; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology / Q000503:physiopathology*; D007395:Interneurons / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000473:pathology / Q000503:physiopathology*; D009415:Nerve Net / Q000473:pathology / Q000503:physiopathology; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011930:Reaction Time / Q000502:physiology; D013003:Somatosensory Cortex / Q000473:pathology / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000502:physiology; D020651:Ventral Thalamic Nuclei / Q000473:pathology / Q000503:physiopathology*