Neurogenesis and neuronal commitment following ischemia in a new mouse model for neonatal stroke

Abstract

Stroke in the neonatal brain is an important cause of neurologic morbidity. To characterize the dynamics of neural progenitor cell proliferation and maturation after survival delays in the neonatal brain following ischemia, we utilized unilateral carotid ligation alone to produce infarcts in postnatal day 12 CD1 mice. We investigated the neurogenesis derived from the sub-ventricular zone and the sub-granular zone of the dentate gyrus subsequent to injury. Newly produced cells were labeled by bromodeoxyuridine at ~1week (P18-20) after the insult by 5 I.P. injections (each 50mg/kg). Subsequent migration and differentiation of the newborn cells was investigated at postnatal day 40 by immunohistochemistry for molecular neuronal and glial cell-lineage markers and BrdU incorporation. Cresyl violet stain demonstrated massive loss of neurons in the ipsilateral septal hippocampus in the CA3 and CA1 regions associated with atrophy. Total counts of new cells were significantly lowered not only in the ipsilateral injured but also the contralateral uninjured hippocampi and correlated with the lesion induced atrophy. Bilateral percent neuronal commitments in the dentate gyri however, were not significantly different from control. New cell densities in the neocortex and striatum increased bilaterally after neonatal stroke. The predominantly non-neuronal commitment of the SVZ derived new cells was similar to the percentage of non-neuronal commitment in controls. In conclusion, neurogenesis occurring at 1 week after neonatal ischemia in the model maintained cell-lineage commitment patterns similar to sham controls. However, the total number of hippocampal SGZ-derived new neurons was reduced bilaterally; in contrast, the SVZ-derived neurogenesis was amplified.

The Endogenous Regenerative Capacity of the Damaged Newborn Brain: Boosting Neurogenesis with Mesenchymal Stem Cell Treatment

“…78,79,83 Furthermore, an increase in BrdU þ cells was observed in the affected SVZ from 1 week to 3 weeks after HI, implying that cell proliferation is stimulated in this region. 14,[77][78][79]81,83,84 Interestingly, BrdU þ cells were also shown in the striatum 14,77,78,81,83 and cortical regions 14,77,82 from 1 to 4 weeks after the insult. This finding suggests that either proliferating cells in the SVZ migrate to these regions or that local progenitors proliferate because of molecular changes in the cell environment.…”

“…Accumulating evidence suggests that HI injury promotes extensive cell proliferation in the SVZ of the rodent brain. 14,[77][78][79][80][81][82][83] Several studies in which P6 and P7 rats and P10 mice were subjected to moderate HI showed that the SVZ expands in size, illustrated by increased cresyl-violet staining and nestin-positive cells in the ipsilateral SVZ. 78,79,83 Furthermore, an increase in BrdU þ cells was observed in the affected SVZ from 1 week to 3 weeks after HI, implying that cell proliferation is stimulated in this region.…”

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

“…Acute postligation seizure activity was scored according to a seizure rating scale as previously reported [6,9].…”

“…Brain atrophy measurements were done as previously described [9] using MCID 7.0 Elite (InterFocus Imaging Ltd.) to measure hemispheric areas of Nissl-stained coronal serial sections spanning rostral striatum to caudal hippocampus (n = 10-12 sections per animal). Total subgranular zone (SGZ) lengths were measured by tracing the SGZ contours using MCID in every DG in which SGZ BrdUpositive cells were quantified.…”

“…A method described previously [9] was used to estimate total counts of If the pup climbs to either end of the string, it has reached ''port'' and is scored by time taken to reach ''port.'' A higher score then indicates lower time taken to travel to the end of the string.…”