The ability of putative neuroprotective compounds to protect against white
matter injury remains poorly investigated due to the lack of suitable metho
ds for assessing white matter injury. This study was therefore designed to
investigate the utility of Tau 1 (oligodendrocytes/axons), myelin basic pro
tein (MBP; myelin) and amyloid precursor protein (APP; axons) immunohistoch
emistry in assessing white matter injury at various times following middle
cerebral artery occlusion (MCAO) in the rat. Focal cerebral ischaemia was i
nduced in halothane-anaesthetised rats using an intraluminal thread model.
At 24 h, 1 and 2 weeks following MCAO, white matter injury was assessed usi
ng Tau 1, APP, MBP and Luxol-fast blue staining and neuronal injury with cr
esyl fast violet (CFV). In histologically normal tissue MBP immunoreactivit
y was detected in myelinated fibre tracts, while Tau I and APP were axonall
y located. At 24 h following permanent MCAO, MBP, and Tau I staining remain
ed relatively unchanged within the myelin and axonal compartments of the is
chaemic region. In contrast, increased Tau 1 staining was apparent in oligo
dendrocytes within ischaemic tissue, while APP accumulated in axons surroun
ding the lesion. At I and 2 weeks following transient MCAO, Tau I and APP s
taining was markedly decreased within ischaemic tissue. Marked reduction in
MBP levels within ischaemic tissue were not detected until 2 weeks followi
ng MCAO. The area of axonal injury as assessed by reduced Tau I or APP stai
ning correlated with the area of neuronal damage as assessed by CFV stainin
g. This study shows that MBP, Tau I and APP immunohistochemistry can be uti
lised to assess myelin and axonal integrity following sustained ischaemia u
sing standard image analysis techniques.