TY - JOUR

T1 - Sensory Stimulation-Induced Astrocytic Calcium Signaling in Electrically Silent Ischemic Penumbra

AU - Murmu, Reena P.

AU - Fordsmann, Jonas C.

AU - Cai, Changsi

AU - Brazhe, Alexey

AU - Thomsen, Kirsten J.

AU - Lauritzen, Martin

PY - 2019

Y1 - 2019

N2 - Middle cerebral artery occlusion (MCAO) induces ischemia characterized by a densely ischemic focus, and a less densely ischemic penumbral zone in which neurons and astrocytes display age-dependent dynamic variations in spontaneous Ca2+ activities. However, it is unknown whether penumbral nerve cells respond to sensory stimulation early after stroke onset, which is critical for understanding stimulation-induced stroke therapy. In this study, we investigated the ischemic penumbra’s capacity to respond to somatosensory input. We examined adult (3- to 4-month-old) and old (18- to 24-month-old) male mice at 2–4 h after MCAO, using two-photon microscopy to record somatosensory stimulation-induced neuronal and astrocytic Ca2+ signals in the ischemic penumbra. In both adult and old mice, MCAO abolished spontaneous and stimulation-induced electrical activity in the penumbra, and strongly reduced stimulation-induced Ca2+ responses in neuronal somas (35–82%) and neuropil (92–100%) in the penumbra. In comparison, after stroke, stimulation-induced astrocytic Ca2+ responses in the penumbra were only moderately reduced (by 54–62%) in adult mice, and were even better preserved (reduced by 31–38%) in old mice. Our results suggest that somatosensory stimulation evokes astrocytic Ca2+ activity in the ischemic penumbra. We hypothesize that the relatively preserved excitability of astrocytes, most prominent in aged mice, may modulate protection from ischemic infarcts during early somatosensory activation of an ischemic cortical area. Future neuroprotective efforts in stroke may target spontaneous or stimulation-induced activity of astrocytes in the ischemic penumbra

AB - Middle cerebral artery occlusion (MCAO) induces ischemia characterized by a densely ischemic focus, and a less densely ischemic penumbral zone in which neurons and astrocytes display age-dependent dynamic variations in spontaneous Ca2+ activities. However, it is unknown whether penumbral nerve cells respond to sensory stimulation early after stroke onset, which is critical for understanding stimulation-induced stroke therapy. In this study, we investigated the ischemic penumbra’s capacity to respond to somatosensory input. We examined adult (3- to 4-month-old) and old (18- to 24-month-old) male mice at 2–4 h after MCAO, using two-photon microscopy to record somatosensory stimulation-induced neuronal and astrocytic Ca2+ signals in the ischemic penumbra. In both adult and old mice, MCAO abolished spontaneous and stimulation-induced electrical activity in the penumbra, and strongly reduced stimulation-induced Ca2+ responses in neuronal somas (35–82%) and neuropil (92–100%) in the penumbra. In comparison, after stroke, stimulation-induced astrocytic Ca2+ responses in the penumbra were only moderately reduced (by 54–62%) in adult mice, and were even better preserved (reduced by 31–38%) in old mice. Our results suggest that somatosensory stimulation evokes astrocytic Ca2+ activity in the ischemic penumbra. We hypothesize that the relatively preserved excitability of astrocytes, most prominent in aged mice, may modulate protection from ischemic infarcts during early somatosensory activation of an ischemic cortical area. Future neuroprotective efforts in stroke may target spontaneous or stimulation-induced activity of astrocytes in the ischemic penumbra

KW - stroke

KW - astrocyes

KW - calcium

KW - ischemic penumbra

KW - sensory stimulation

U2 - 10.3389/fnagi.2019.00223

DO - 10.3389/fnagi.2019.00223

M3 - Journal article

C2 - 31496947

VL - 11

JO - Frontiers in Aging Neuroscience

JF - Frontiers in Aging Neuroscience

SN - 1663-4365

M1 - 223

ER -