Microtubule‐associated protein 2, an early blood marker of ischemic brain injury

Abstract

The aim of this study was to develop a sensitive and rapid blood marker to detect ischemic brain injury, because imaging techniques have a limited capacity to identify lesions during the first crucial hours without massive tissue destruction. Rats were subjected to middle cerebral artery occlusion for various durations (0.5-3 hr), followed by reperfusion. At different time points after ischemia and/or ischemia-reperfusion, the amounts of glial fibrillary acidic protein (GFAP) and microtubule-associated protein 2 (MAP2) in the cerebrospinal fluid (CSF) and serum were analyzed by Western blotting. Brain infarction was observed in an ischemia-duration-dependent manner. GFAP was drastically increased in the CSF 24 and 48 hr after reperfusion, without change in the serum level. Serum levels of MAP2 remarkably increased as early as 0.5 hr of ischemia, much earlier than the observation of minimal tissue injury 3 hr following occlusion. The serum MAP2 level was further increased by a short period (2 hr) of reperfusion, even in 0.5- and 1-hr ischemic rats, despite not observing any typical tissue injuries 24 hr after reperfusion. These results indicate that the MAP2 protein may be able to detect early neuronal injuries, because the level of this protein in the blood spikes before the appearance of visible macrolesions. Therefore, MAP2 could potentially be used as a novel early marker for the detection of a neurotoxic insult.

Increased levels of serum MAP-2 at 6-months correlate with improved outcome in survivors of severe traumatic brain injury

“…Although previous studies conducted in the acute and sub-acute phase after ischemia, hypoxia and TBI have demonstrated that MAP-2 disappear in damaged brain regions and that serum MAP-2 levels increase early following injury [12][13][14], little is known about its role and potential use in the later chronic phase after TBI. As a chronic biomarker, MAP-2 could provide relevant information about the developing pathophysiological mechanisms of neuronal remodelling that can help to shape pharmacological interventions and rehabilitation approaches.…”

Comparative effects of plant oils and trans-fat on blood lipid profiles and ischemic stroke in rats

“…Focal cerebral ischemia, through middle cerebral artery occlusion (MCAO) surgery, was produced as described previously [ 28 ] , with slight modification [ 27, 29 ] . In brief, under anesthesia of the rats with isoflurane, a midline incision was made on the ventral side of the neck, exposing the left common carotid artery (CCA), external carotid artery (ECA), and internal carotid artery (ICA).…”

Biomarkers of Traumatic Brain Injury in the Geriatric Population

“…Candidates thus far include neural cell body injury markers such as neuron-specific enolase (NSE,) and ubiquitin C-terminal hyrdrolase-1 (UCH-L1) [9•, 39, 40••]; gliosis and/or glial injury markers S100β (calciumbinding protein localized to glial cells) and glial fibrillary acidic protein (GFAP) [33,34,41••]; the demyelination indicator myelin basic protein (MBP) [20]; indicators of axonal injury such as axonal microtubule associated protein (Tau, or cleaved Tau) [35] and neurofilament protein-H and -L (NF-H) [36,37,39]; dendritic injury marker microtubule associated protein-2 (MAP-2) [38]; and a number of proinflammatory cytokines such as interleukins 1, 6, and 8 (IL-1, IL-6, IL-8), tumor necrosis factor alpha (TNFα), and interferon gamma (IFN-γ) [42,43]. AlphaII-spectrin, a major substrate for both calpain and caspase-3 is also a promising marker [19,39]. Its breakdown products include spectrin breakdown product (SBDP)-150 and SBDP-145 from calpain activation (primary during acute necrotic neuronal injury or death) and SBDP-120 from caspase-3 proteolysis seen during the delayed apoptosis stage [21,22].…”