Abstract
Neurological deterioration of intracerebral hemorrhage (ICH) mostly occurs within the first 24 hours. Together with the microglia/macrophages (MMΦ), astrocytes are important cell population responsible for many brain injuries but rarely being highlighted in acute stage of ICH. In present study, we induced rats ICH either by collagenase or autologous blood injection. Experimental groups were classified as vehicle or Ethyl-1-(4-(2,3,3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate (Pyr3) treatment group (n = 9, each group). MRI assessments after ICH were used to evaluate the hematoma progression and blood–brain barrier (BBB) integrity. The glia cells accumulations were examined by GFAP and Iba1 immunohistochemistry, respectively. Abundant astrocytes but few MMΦ were observed in hyperacute and acute ICH. Upon suppression of astrocyte activity, ICH rats exhibited decreased size of hematoma expansion, less BBB destruction, reduced astrocyte accumulation in perihematomal regions, postponed course of hemoresolution and gain better outcomes. These finding provide evidence that activated astrocytes are crucial cell populations in hyperacute and acute ICH, and their modulation may offer opportunities for novel therapy and patient management.
Highlights
Most neurological deterioration of intracerebral hemorrhage (ICH) occurs within the first 24 h and is defined as either hyperacute or acute stages of ICH [1, 2]
Astrocytes act as the major cell population within the first 24 h of ICH rather than microglia or macrophages
Astrocyte activity was decreased using Pyr3; the activated astrocytes affected the lesion size, hematoma resolution, and blood– brain barrier (BBB) destruction. These findings support the notion that reactive www.impactjournals.com/oncotarget www.impactjournals.com/oncotarget astrocytes play a crucial role in the hyperacute and acute stages of ICH
Summary
Most neurological deterioration of intracerebral hemorrhage (ICH) occurs within the first 24 h and is defined as either hyperacute (within 3 h) or acute (within 24 h) stages of ICH [1, 2]. From the initial hours of onset to the first few days after ICH onset, inflammatory responses are a critical concern, which are dominated by the resident www.impactjournals.com/oncotarget astrocytes and microglia and the peripheral neutrophils and macrophages [4, 5]. Among these cells, the reactive astrocytes accumulate in the perihematomal region as early as 1–3 days after ICH onset, which is much earlier than the accumulation of microglia and macrophages (3–7 days after ICH) [6]. The role of astrocytes within the first 24 h of ICH has not been fully addressed
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