Pre-conditioning with transcranial low-level light therapy reduces neuroinflammation and protects blood-brain barrier after focal cerebral ischemia in mice.

PURPOSE: Transcranial low-level light therapy (LLLT) has gained interest as a non-invasive, inexpensive and safe method of modulating neurological and psychological functions in recent years. This study was designed to examine the preventive effects of LLLT via visible light source against cerebral ischemia at the behavioral, structural and neurochemical levels. METHODS: The mice received LLLT twice a day for 2 days prior to photothrombotic cortical ischemia. RESULTS: LLLT significantly reduced infarct size and edema and improved neurological and motor function 24 h after ischemic injury. In addition, LLLT markedly inhibited Iba-1- and GFAP-positive cells, which was accompanied by a reduction in the expression of inflammatory mediators and inhibition of MAPK activation and NF-κB translocation in the ischemic cortex. Concomitantly, LLLT significantly attenuated leukocyte accumulation and infiltration into the infarct perifocal region. LLLT also prevented BBB disruption after ischemic events, as indicated by a reduction of Evans blue leakage and water content. These findings were corroborated by immunofluorescence staining of the tight junction-related proteins in the ischemic cortex in response to LLLT. CONCLUSIONS: Non-invasive intervention of LLLT in ischemic brain injury may provide a significant functional benefit with an underlying mechanism possibly being suppression of neuroinflammation and reduction of BBB disruption.

Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke.

Neural stem cell (NSC) transplantation has been investigated as a means to reconstitute the damaged brain after stroke. In this study, however, we investigated the effect on acute cerebral and peripheral inflammation after intracerebral haemorrhage (ICH). NSCs (H1 clone) from fetal human brain were injected intravenously (NSCs-iv, 5 million cells) or intracerebrally (NSCs-ic, 1 million cells) at 2 or 24 h after collagenase-induced ICH in a rat model. Only NSCs-iv-2 h resulted in fewer initial neurologic deteriorations and reduced brain oedema formation, inflammatory infiltrations (OX-42, myeloperoxidase) and apoptosis (activated caspase-3, TUNEL) compared to the vehicle-injected control animals. Rat neurosphere-iv-2 h, but not human fibroblast-iv-2 h, also reduced the brain oedema and the initial neurologic deficits. Human NSCs-iv-2 h also attenuated both cerebral and splenic activations of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and nuclear factor-kappa B (NF-kappaB). However, we observed only a few stem cells in brain sections of the NSCs-iv-2 h group; in the main, they were detected in marginal zone of spleens. To investigate whether NSCs interact with spleen to reduce cerebral inflammation, we performed a splenectomy prior to ICH induction, which eliminated the effect of NSCs-iv-2 h transplantation on brain water content and inflammatory infiltrations. NSCs also inhibited in vitro macrophage activations after lipopolysaccharide stimulation in a cell-to-cell contact dependent manner. In summary, early intravenous NSC injection displayed anti-inflammatory functionality that promoted neuroprotection, mainly by interrupting splenic inflammatory responses after ICH.

Intracranial pressure and outcome in adult encephalitis.

The relationship between intracranial pressure (ICP) and outcome was studied in 10 adults with encephalitis. Eight had biopsy-proven herpes simplex encephalitis, one had acute hemorrhagic leukoencephalitis, and in one case the cause of encephalitis was unknown. Monitoring of ICP was instituted because of clinical deterioration or computerized tomography evidence of brain swelling, and was begun a mean of 7 days after the onset of symptoms and continued for a mean of 9 days. All five survivors, but only one of the five fatalities, had an initial ICP of less than 12 mm Hg (p less than 0.05). Four patients with a mean daily ICP of less than 20 mm Hg survived, whereas five of six patients with higher ICP's died (p less than 0.05). Peak ICP did not occur until the 12th day of illness on average. The Glasgow Coma Scale score at the time the ICP monitor was inserted did not correlate with outcome. Intracranial pressure monitoring in severe encephalitis may be a useful adjunct for therapy and an indicator of prognosis.