The potential role of inflammatory mechanisms in the pathophysiology of ischemic brain damage has intensely been discussed. We have recently demonstrated that stroke patients display an intrathecal production of proinflammatory cytokines early after onset of symptoms. IL-1beta, one of these cytokines, stimulates the production of nitric oxide (NO), a potent inflammatory mediator. The aim of the present study was to investigate the intrathecal levels of nitrate, one of the main metabolites of NO in acute stroke and to relate its levels to brain damage. Stroke patients were prospectively studied with clinical evaluation, radiological assessment and analysis of intrathecal levels of nitrate by gas chromatography/mass spectrometry. In addition, simultaneous analyses of cytokines and of soluble Fas/APO-1 and bcl-2, two proteins regulating apoptosis, were performed. The intrathecal levels of nitrate were not significantly different in stroke patients compared to controls throughout the observation period. However, the intrathecal levels of nitrate increased significantly 3 months after stroke onset compared with the first 3 days. Interestingly, the levels of nitrate measured at stroke onset were negatively correlated to the final size of infarct volume (r = -0.69, p < 0.05) measured by MRI. In addition, patients with large infarcts displayed significantly (p = 0.008) lower levels of nitrate in cerebrospinal fluid compared to patients with small infarcts during the first 3 days after stroke onset. In contrast, the intrathecal levels of nitrate were significantly positively correlated (r = 0.79, p < 0. 001) to the neurological deficit and negatively correlated (r = -0. 76, p < 0.05) to bcl-2, a protein downregulating neuronal apoptosis, in the late stage of the stroke. Early NO production is associated with a smaller infarct volume, suggesting a protective effect, whereas late NO production is associated with severer neurological deficits, suggesting a neurotoxic effect. Treatment trials pertaining to modulate NO production in stroke should take into consideration the dual effect of NO on ischemic brain damage.

Adult↗

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Cerebrospinal fluid markers of pathogenetic processes in vascular dementia, with special reference to the subcortical subtype.

There is a need for improvement of the diagnosis of vascular dementia (VaD). Today, the clinician has to rely on clinical examination, history, and, possibly, brain imaging to identify cerebrovascular damage and other signs of VaD. The clinical diagnosis of subcortical VaD may be difficult because the clinical manifestation of this disorder is often similar to that of Alzheimer disease. There are also mixed forms of the two disorders. Biochemical diagnostic markers, which reflect the pathogenetic processes in the brain, would add to the accuracy of the diagnosis. There are some interesting candidate markers: the cerebrospinal fluid (CSF)/serum albumin ratio could be used to identify blood-brain barrier damage to the small intracerebral vessels, CSF sulfatide to identify ongoing demyelination of the white matter, CSF neuron-specific enolase to identify ongoing neuronal degeneration, and CSF tau protein and CSF neurofilament light protein to identify ongoing axonal degeneration. None of these potential markers is specific to subcortical VaD, but together and used in conjunction with the conventional diagnostic workup, they may be of diagnostic value.

Alzheimer Disease↗