A Distinct Boundary between the Higher Brain’s Susceptibility to Ischemia and the Lower Brain’s Resistance

Abstract

Higher brain regions are more susceptible to global ischemia than the brainstem, but is there a gradual increase in vulnerability in the caudal-rostral direction or is there a discrete boundary? We examined the interface between `higher` thalamus and the hypothalamus the using live brain slices where variation in blood flow is not a factor. Whole-cell current clamp recording of 18 thalamic neurons in response to 10 min O2/glucose deprivation (OGD) revealed a rapid anoxic depolarization (AD) from which thalamic neurons do not recover. Newly acquired neurons could not be patched following AD, confirming significant regional thalamic injury. Coinciding with AD, light transmittance (LT) imaging during whole-cell recording showed an elevated LT front that initiated in midline thalamus and that propagated into adjacent hypothalamus. However, hypothalamic neurons patched in paraventricular nucleus (PVN, n= 8 magnocellular and 12 parvocellular neurons) and suprachiasmatic nucleus (SCN, n= 18) only slowly depolarized as AD passed through these regions. And with return to control aCSF, hypothalamic neurons repolarized and recovered their input resistance and action potential amplitude. Moreover, newly acquired hypothalamic neurons could be readily patched following exposure to OGD, with resting parameters similar to neurons not previously exposed to OGD. Thalamic susceptibility and hypothalamic resilience were also observed following ouabain exposure which blocks the Na+/K+ pump, evoking depolarization similar to OGD in all neuronal types tested. Finally, brief exposure to elevated [K+]o caused spreading depression (SD, a milder, AD-like event) only in thalamic neurons so SD generation is regionally correlated with strong AD. Therefore the thalamus-hypothalamus interface represents a discrete boundary where neuronal vulnerability to ischemia is high in thalamus (like more rostral neocortex, striatum, hippocampus). In contrast hypothalamic neurons are comparatively resistant, generating weaker and recoverable anoxic depolarization similar to brainstem neurons, possibly the result of a Na/K pump that better functions during ischemia.

Cerebroprotective activity of Pentapetes phoenicea on global cerebral ischemia in rats

“…[14] Among various brain regions, some are more susceptible to brain ischemia due to the high rate of oxidative metabolic activity, intense production of reactive oxygen metabolites, high content of polyunsaturated fatty acids, relatively low antioxidant capacity, low repair mechanism activity, and poor plasticity in that areas. [15]…”

Activation of the ACE2/Ang-(1–7)/Mas pathway reduces oxygen–glucose deprivation-induced tissue swelling, ROS production, and cell death in mouse brain with angiotensin II overproduction

“…In ischemia, the magnitude of the change in tissue water content is dependent on the degree of brain injury 56 . Changes in brain extracellular or intracellular water content as a result of exposure to aniso-osmotic, hypoxic, or ischemic conditions alter the optical properties of the tissue, measured here as the IOS 1, 9, 30, 41 . In the present studies, we found a consistent increase in IOS in slices from SARA mice during OGD, similar to our previous studies using brain slices from wild type and R+A+ mice 13 .…”

“…Tissue swelling as a measure of brain edema was determined indirectly as we and others previously described 5, 9, 51 by measuring the intrinsic optical signal (IOS) defined as the intensity of transmitted light during OGD treatment expressed as a percent of the intensity measured prior to the start of OGD 5 . Slices were transilluminated using a DC-regulated halogen lamp which delivered white light to the recording stage via a randomized fiber optic bundle.…”

Fatal mechanical asphyxia induces changes in energy utilization in the rat brain: An 18F-FDG–PET study

“…⁄ p < 0.05, significant; ⁄⁄ p < 0.01, very significant; ⁄⁄⁄ p < 0.001, extremely significant. thalamus-hypothalamus interface represents a discrete boundary, with high thalamic neuronal vulnerability to ischemia (as in the more rostral neocortex, striatum, and hippocampus), and low vulnerability in the hypothalamus (as in the brainstem) [39]. Thus, decreased FU may correlate with increased tolerance to asphyxia.…”