Poststroke subgranular and rostral subventricular zone proliferation in a mouse model of neonatal stroke

Abstract

Stroke in the neonatal brain is an understudied cause of neurologic morbidity. Recently we have characterized a new immature mouse model of stroke utilizing unilateral carotid ligation alone to produce infarcts and acute seizures in postnatal day 12 (P12) CD-1 mice. In this study, the amount of poststroke neural progenitor proliferation was examined in the subgranular (SGZ) of the dentate gyrus and the subventricular zone (SVZ) 7, 14, and 21 days after ischemia (DAI). A single IP injection (50 mg/kg) of bromodeoxyuridine (BrdU) given 2 hr before perfusion fixation labeled newborn cells. Early cell pheno-types were quantified by colabeling with GFAP, nestin, and DCX. Control mice revealed an age-dependent decrease in neural proliferation, with an ~50% drop in BrdU-labeled cell counts at P33 compared with P19 both in the SGZ and in the SVZ. Significant reduction in the amount of neural proliferation in the ipsilateral injured SGZ of ligated mice correlated with both the severity of the stroke-injury and the acute seizure scores. Similar correlations were not detected contralaterally. Contralateral SGZ neural proliferation was initially lowered at 7 DAI but normalized by 21 DAI. In both injured and control brains, ~90% of newborn SGZ cells colabeled with nestin, ~30% colabeled with GFAP, and a few colabeled with DCX. In contrast, poststroke SVZ cell proliferation was enhanced ipsi- more than contralaterally at 7 DAI. In the SVZ, the enhanced neural proliferation normalized to control levels by P33. In conclusion, the neural cell proliferation was differentially altered in the SGZ vs. SVZ after neonatal stroke.

Different effects of high- and low-dose phenobarbital on post-stroke seizure suppression and recovery in immature CD1 mice

“…Chen et al (Chen et al, 2009) corroborated these decreases in hippocampal neurogenesis after chronic administration to neonatal rats, and also reported a conservation of the relative proportions of newborn neuronal and glial cell types. It is possible that these are model-dependent differences: the experiments cited previously were performed in naïve rodents, while our ischemia model has already demonstrated suppressed neurogenesis in the DG after the stroke event (Kadam et al, 2008; Kadam et al, 2009a). It is also possible that a single dose is not enough to induce these changes in neurogenesis in the period investigated in this study.…”

“…This model has been demonstrated to produce acute behavioral seizures, functional deficits, impaired neurogenesis and brain injury (Comi et al, 2004; Kadam et al, 2008; Kadam et al, 2009a; Kadam et al, 2009b). We report here the impact of a single acute dose of phenobarbital (30 mg/kg or 60 mg/kg) upon these endpoints after stroke in the immature brain.…”

Systemic Injection of CD34+-Enriched Human Cord Blood Cells Modulates Poststroke Neural and Glial Response in a Sex-Dependent Manner in CD1 Mice

“…Images inverted in Adobe Photoshop CS4 software (Adobe Systems Incorporated) granularly segmented to separate GFAP-positive area from GFAP-negative area and then the immunopositive area in each region of interest was measured ( Stacks of 1 mm thick images of BrdU and GFAP in the subventricular zone (SVZ) region were taken on an Olympus FV 1000 laser scanning confocal system at bregma coordinates level 0.74 to 1.18 mm [12]. Images were analyzed using Image J (U.S. National Institutes of Health; http://rsb.info.nih.gov/ij/, 1997-2006) software to arbitrarily quantify BrdU, and GFAP expression, in the region of the SVZ of ligated and control brains as previously reported [13]. The SVZ region was further subdivided into the SVZ proper, the white matter above the SVZ, and the striatum below the SVZ, and BrdU and GFAP labeling was quantified in these regions using MCID; standardized distances from the SVZ (Fig.…”

Altered Postnatal Cell Proliferation in Brains of Mouse Pups Prenatally Exposed to IgG from Mothers of Children with Autistic Disorder

“…In its place, we measured the area of the packed BrdU-positive cells in the SVZ horn (ie, using the green channel for BrdU-positive cells only; Fig. 2A), the expansion of which has been shown to represent increased proliferation in many rodent models of brain development, injury, and inflammation 14–16. SVZ areas (ie detected by borders of tightly packed BrdU-labeled cells) were significantly larger in the MCAD-IgG-treated group than in both the MUC IgG and PBS controls.…”