Post-stroke gaseous hypothermia increases vascular density but not neurogenesis in the ischemic penumbra of aged rats

TY - JOUR

T1 - Post-stroke gaseous hypothermia increases vascular density but not neurogenesis in the ischemic penumbra of aged rats

AU - Sandu, Raluca Elena

AU - Uzoni, Adriana

AU - Ciobanu, Ovidiu

AU - Moldovan, Mihai

AU - Anghel, Andrei

AU - Radu, Eugen

AU - Coogan, Andrew N.

AU - Popa-Wagner, Aurel

PY - 2016

Y1 - 2016

N2 - Purpose: In aged humans, stroke is a major cause of disability for which no neuroprotective measures are available. In animal studies of focal ischemia, short-term hypothermia often reduces infarct size. Nevertheless, efficient neuroprotection requires long-term, regulated lowering of whole body temperature. Previously, we reported that post-stroke exposure to hydrogen sulfide (H2S) effectively lowers whole body temperature and confers neuroprotection in aged animals. Methods: In the present study using behavioral tests, MRI, telemetrical EEG, BP and temperature recordings, RT-PCR and immunofluorescence, we assessed infarct size, vascular density, neurogenesis and as well as the expression of genes coding for proteasomal proteins as well as in post-stroke aged Sprague-Dawley rats exposed to H2S- induced hypothermia. Results: Two days exposure to mild hypothermia diminishes the expression of several genes involved in protein degradation, thereby leading to better preservation of infarcted tissue. Further, hypothermia increased the density of newly formed blood vessels in the peri-lesional cortex did not enhance neurogenesis in the infarcted area of aged rats. Likewise, there was improved recovery of fine vestibulomotor function and asymmetric sensorimotor deficit. Conclusion: Long-term hypothermia may be a viable clinical approach by simultaneously targeting multiple processes including better tissue preservation, enhanced vascular density and improved behavioral performance.

AB - Purpose: In aged humans, stroke is a major cause of disability for which no neuroprotective measures are available. In animal studies of focal ischemia, short-term hypothermia often reduces infarct size. Nevertheless, efficient neuroprotection requires long-term, regulated lowering of whole body temperature. Previously, we reported that post-stroke exposure to hydrogen sulfide (H2S) effectively lowers whole body temperature and confers neuroprotection in aged animals. Methods: In the present study using behavioral tests, MRI, telemetrical EEG, BP and temperature recordings, RT-PCR and immunofluorescence, we assessed infarct size, vascular density, neurogenesis and as well as the expression of genes coding for proteasomal proteins as well as in post-stroke aged Sprague-Dawley rats exposed to H2S- induced hypothermia. Results: Two days exposure to mild hypothermia diminishes the expression of several genes involved in protein degradation, thereby leading to better preservation of infarcted tissue. Further, hypothermia increased the density of newly formed blood vessels in the peri-lesional cortex did not enhance neurogenesis in the infarcted area of aged rats. Likewise, there was improved recovery of fine vestibulomotor function and asymmetric sensorimotor deficit. Conclusion: Long-term hypothermia may be a viable clinical approach by simultaneously targeting multiple processes including better tissue preservation, enhanced vascular density and improved behavioral performance.

KW - Aging

KW - HS

KW - hypothermia

KW - neurogenesis

KW - proteasome

KW - stroke

KW - vascular density

U2 - 10.3233/RNN-150600

DO - 10.3233/RNN-150600

M3 - Journal article

C2 - 26923618

AN - SCOPUS:84975492973

SN - 0922-6028

VL - 34

SP - 401

EP - 414

JO - Restorative Neurology and Neuroscience

JF - Restorative Neurology and Neuroscience

IS - 3

ER -