ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract : Diffuse axonal injury is a primary feature of head traumaand is one of the most frequent causes of mortality and morbidity. Diffuseaxonal injury is microscopic in nature and difficult or impossible to detectwith imaging techniques. The objective of the present study was to determinewhether axonal injury in head trauma patients could be quantified by measuringlevels of CSF tau proteins. Tau proteins are structural microtubule bindingproteins primarily localized in the axonal compartment of neurons. Monoclonalantibodies recognizing the form of tau found in the CSF of head traumapatients were developed by differential CSF hybridoma screening using CSF fromhead trauma and control patients. Clones positive for head trauma CSF tauproteins were used to characterize this form of tau and for ELISA development.Using the developed ELISA, CSF tau levels were elevated 〉1,000-fold in headtrauma patients (mean, 1,519 ng/ml of CSF) when compared with patients withmultiple sclerosis (mean, 0.014 ng/ml of CSF ; p 〈 0.001), normalpressure hydrocephalus (nondetectable CSF tau), neurologic controls (mean,0.031 ng/ml of CSF ; p 〈 0.001), or nonneurologic controls(nondetectable CSF tau ; p 〈 0.001). In head trauma, a relationship between clinical improvement and decreased CSF tau levels was observed. These data suggest that CSF tau levels may prove a clinically useful assay for quantifying the axonal injury associated with head trauma and monitoring efficacy of neuroprotective agents. Affinity purification of CSF tau from head trauma patients indicated a uniform cleavage of ~ 18 kDa from all six tau isoforms, reducing their apparent molecular sizes to 30-50 kDa. These cleaved forms of CSF tau consisted of the interior portion of the tau sequence, including the microtubule binding domain, as judged by cyanogen bromide digestion. Consistent with these data, CSF cleaved tau bound taxolpolymerized microtubules, indicating a functionally intact microtubule binding domain. Furthermore, epitope mapping studies suggested that CSF cleaved tau proteins consist of the interior portion of the tau sequence with cleavage at both N and C terminals.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1999.0720741.x
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