Glial activation in white matter following ischemia in the neonatal P7 rat brain.
This study examines cell death and proliferation in the white matter after neonatal stroke. In postnatal day 7 injured rat, there was a marked reduction in myelin basic protein (MBP) immunostaining mainly corresponding to numerous pyknotic immature oligodendrocytes and TUNEL-positive astrocytes in the ipsilateral external capsule. In contrast, a substantial restoration of MBP, as indicated by the MBP ratio of left-to-right, occurred in the cingulum at 48 (1.27 +/- 0.12) and 72 (1.30 +/- 0.18, P < 0.05) h of recovery as compared to age-matched controls (1.03 +/- 0.14). Ki-67 immunostaining revealed a first peak of newly generated cells in the dorsolateral hippocampal subventricular zone and cingulum at 72 h after reperfusion. Double immunofluorescence revealed that most of the Ki-67-positive cells were astrocytes at 48 h and NG2 pre-oligodendrocytes at 72 h of recovery. Microglia infiltration occurs over several days in the cingulum, and a huge quantity of macrophages reached the subcortical white matter where they engulfed immature oligodendrocytes. The overall results suggest that the persistent activation of microglia involves a chronic component of immunoinflammation, which overwhelms repair processes and contributes to cystic growth in the developing brain.
Biran
Valérie
V
UMR-CNRS 7102, Université Pierre et Marie Curie, HICD, case 14, 9 quai St-Bernard, 75005 Paris, France; Service de Néonatologie, Hôpital Armand Trousseau, 75012 Paris, France.
Joly
Luc-Marie
LM
Héron
Anne
A
Vernet
Agnès
A
Véga
Céline
C
Mariani
Jean
J
Renolleau
Sylvain
S
Charriaut-Marlangue
C
C
D000818:Animals; D000831:Animals, Newborn; D000941:Antigens / Q000378:metabolism; D001921:Brain / Q000254:growth & development / Q000502:physiology*; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology; D002452:Cell Count / Q000379:methods; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D007839:Functional Laterality / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000379:methods; D007511:Ischemia / Q000150:complications / Q000473:pathology*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D004676:Myelin Basic Protein / Q000378:metabolism; D009457:Neuroglia / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D018709:Statistics, Nonparametric; D013997:Time Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D004676:Myelin Basic Protein; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4