Brain Injury review

This abstract comes from Q Guan and colleagues from the Zhang lab at the Xuzhou Medical College in Taiwan.

Our previous studies and the others have strongly suggested that -Jun N-terminal kinase signaling pathway plays a critical role in ischemic brain injury. Here, we reported that SP600125, a potent, cell-permeable, selective, and reversible inhibitor of c-Jun N-terminal kinase, potently decrease neuronal apoptosis induced by global ischemia/reperfusion in the vulnerable hippocampal CA1 subregion.

As a result, SP600125 diminished the increased phosphorylation of c-Jun and the increased expression of FasL induced by ischemia/reperfusion in the vulnerable hippocampal CA1 subregion. At the same time, through inhibiting phosphorylation of Bcl-2 and the release of Bax from Bcl-2/Bax dimers, SP600125 attenuated Bax translocation to mitochondria and the release of cytochrome c induced by ischemia/reperfusion (I/R). Furthermore, the activation of caspase-3 induced by ischemia/reperfusion was also significantly suppressed by preinfusion of SP600125. Importantly, the same neuropotective effect was showed by administration of SP600125 both before and after ischemia.

Thus, our findings imply that SP600125 can inhibit the activation of-Jun N-terminal kinase signaling pathway and induce neuroprotection against ischemia/reperfusion in rat hippocampal CA1 region via suppressing the extrinsic and intrinsic pathways of apoptosis. Taken together, these results indicate that targeting the c-Jun N-terminal kinase pathway provides a promising therapeutic approach for ischemic brain injury.

The pubmed identifier for this abstract is 16674927. It is in the may 2006 edition of Brain Research.

This abstract is by R. Pluta, M. Ulamak and S. Januszewski from the dept. of neurodegenerative disorders at the Polish Academy of Science in Warsaw.

Our study demonstrates that ischemia-reperfusion brain injury induces an increase in blood brain barrier permeability in the periventricular white matter. This chronic insufficiency of blood brain barrier may allow entry of neurotoxic fragments of amyloid precursor protein and other blood components such as platelets into the perineurovascular white matter tissue.

These components may have secondary and chronic harmful effects on the ischemic myelin and axons and can intensify the phagocytic activity of microglial cells. Pathological accumulation of toxic fragments of amyloid precursor proteinin myelinated axons and oligodendrocytes appears after ischemic blood brain barrier injury and seem to be concomitant with, but independent of neuronal injury. It seems that ischemia-reperfusion disturbances may play important roles, both directly and indirectly, in the pathogenesis of white matter lesions. This pathology appears to have distribution similar to that of sporadic Alzheimer’s disease. We noted micro blood brain barrier openings in ischemic white matter lesions that probably would act as seeds of future Alzheimer’s-type pathology.

This abstract is available from pubmed using the identifier 16671468. The full articlu is available in the May 2006 issue of Acta Neurochirurgica starting on page 267.

This article on ischaemic brain injury by Mcloone and colleagues is from

The British Journal of Ophthalmolgy and looked into increased incidence of optic nerve hypoplasia in infants.

The aims were to evaluate the role of optic disc morphology in dating ischaemic brain injurys in infants.

They analysed 109 premature infants by use of cranial ultrasounds and magnetic resonance imaging. The group wss divided into groups of those with periventricular leucomalacia and intraventricular haemorrhage those without, the control group contained infants with normal neuroimaging at term and at the age of two.

‘Using the image analysis software of the RetCam, optic disc diameter (ODD), optic disc area (ODA), and optic cup area (OCA) were measured at 33-34 weeks gestational age. As serial cranial ultrasonography had been performed, it was possible to date the brain injury in those infants with periventricular white matter (PVWM) damage.’

‘RESULTS: Although there was a trend towards reducing ODD, ODA, and OCA with increasing severity of IVH, only the IVH 4 group differed significantly from the controls for these parameters (p = 0.002, p = 0.02, and p = 0.04, respectively). 44.4% of infants with grade 4 IVH had small discs. Only one patient had a large cup in a normal sized disc; this patient had IVH 4. In patients with PVWM damage, the median time of insult was 27 weeks in those with small discs and 28 weeks in those with normal discs. This difference was not significant (p = 0.23).’

‘CONCLUSIONS: Premature infants with IVH 4 have an increased incidence of optic nerve hypoplasia. We found no association between disc morphology and timing of brain injury.’

The full article can be found via pubmed    PMID: 16547329 [PubMed - as supplied by publisher]