Rotational acceleration of the head, as occurs in falls, car crashes, and sport injuries, may result in diffuse brain damage, with acute and chronic neurological and psychiatric symptoms. The present study addresses the effects of rotational trauma on the neuronal cytoskeleton, which stabilizes perikaryal, dendritic and axonal shape and function. The study focuses upon the distribution of (1) the phosphorylated form of the heavy neurofilament subunit, (2) the light neurofilament subunit, and (3) beta-amyloid, a marker for brain injury. While normally restricted to axons, the phosphorylated heavy neurofilament subunits were drastically decreased in the axons after rotational trauma. Instead, they accumulated in the neuronal perikarya, normally devoid of the phosphorylated subunit. This alteration was seen, not only in the cerebral cortex, but also in the hippocampus, the cervical spinal cord, the cerebellum, the cranial nerves and the pyramidal tract. The distribution of the light subunit of neurofilaments was also altered post trauma. Only a weak beta-amyloid immunoreactivity was detected in the brains of control animals. Promptly after the trauma, a large number of beta-amyloid positive neurons appeared. Intensely co-localized immunoreactivity for the light subunit of neurofilaments and of beta-amyloid was seen 3 days after the rotational trauma axons of in the subcortical white matter and in the granule cell layer of the dentate gyrus as well as in neurons of the hypoglossal nucleus. The reported alterations in the central nervous system neurons are similar to those in the human brain after closed head injury and in chronic degenerative diseases. Regions of importance for social behavior, memory and body movement were affected.

Cell specific markers were quantified in the hippocampus, the amygdala/pyriform cortex, the frontal cerebral cortex and the striatum of the rat brain after systemic administration of kainic acid. Neuron specific enolase (NSE) reflects loss of neurons, glial fibrillary acidic protein (GFAP) reflects reactive gliosis, and brain levels of serum proteins measures blood-brain-barrier permeability. While the concentration of NSE remained unaffected in the frontal cerebral cortex and the striatum, their GFAP content increased during the first three days. In the hippocampus and amygdala, NSE levels decreased significantly. GFAP levels in the hippocampus were unaffected after one day and decreased in the amygdala/pyriform cortex. After that, GFAP increased strikingly until day 9 or, in the case of amygdala/pyriform cortex, even longer. This biphasic time course for GFAP was accompanied by a decrease of S-100 during days 1-9 followed by a significant increase at day 27 above the initial level. The regional differences in GFAP and S-100 could result from the degree of neuronal degeneration, the astrocytic receptor set-up and/or effects on the blood-brain barrier.

Astrocytes maintain their volume in response to changes in osmotic pressure in their environment by an afflux/influx of ions and organic osmoequivalents. The initial swelling of an astrocyte transferred to a hypoosmotic medium is thus reversed within minutes. The mechanisms which trigger this process as well as the sensors for cell volume are largely unknown, however, the cytoskeleton appears to be involved. We have addressed the role of one component of the cytoskeleton, the intermediate filaments, in the maintenance of astrocytic cell volume. Astrocytes from wild type mice were compared with cells from mice deficient for either glial fibrillary acidic protein (GFAP-/-) or vimentin (vimentin-/-) and with astrocytes from mice deficient for both proteins (GFAP-/-vim-/-). Whereas GFAP-/- and vimentin-/- cultured or reactive astrocytes retain intermediate filaments, the GFAP-/-vim-/- astrocytes are completely devoid of these structures. The rate of efflux of the preloaded osmoequivalent 3H-taurine from primary and passaged cultures of astrocytes was monitored. A reduction of NaCl (25 mM) in the perfusion medium led to a 400-900% increase of 3H-taurine afflux in astrocytes from wild type mice. The stimulated efflux was not significantly affected in astrocytes from GFAP-/- or vimentin-/- mice. However, the efflux from astrocytes from GFAP-/-vim-/- mice was 25-46% lower than the wild type levels. The results strengthen the role of the cytoskeleton in astrocyte volume regulation and suggest an involvement of intermediate filaments in the process.