Changes of extracellular space volume and tortuosity in the spinal cord
of Lewis rats with experimental autoimmune encephalomyelitis.
Simonova Z, Svoboda J, Orkand P, Bernard CC, Lassmann H, Sykova E
Department of Cellular Neurophysiology, Academy of Sciences of the Czech
Republic, Prague, Czech Republic.
Three diffusion parameters of nervous tissue, extracellular space (ECS)
volume fraction (alpha), tortuosity (gamma) and non-specific uptake (k')
of tetramethylammonium (TMA+), were studied in the spinal cord of rats
during experimental autoimmune encephalomyelitis (EAE). The three parameters
were determined in vivo from concentration-time profiles of TMA+ using
ion-selective microelectrodes. EAE was induced by injection of guinea-pig
myelin basic protein (MBP), which resulted in typical morphological changes
in the CNS tissue, namely inflammatory reaction, astrogliosis, blood-brain
barrier (BBB) damage and paralysis. EAE was accompanied by a statistically
significant increase of alpha (mean +/- S.E.M.) in the dorsal horn from
0.21 +/- 0.01 to 0.28 +/- 0.02, in the intermediate region from 0.22 +/-
0.01 to 0.33 +/- 0.02, in the ventral horn from 0.23 +/- 0.01 to 0.47 +/-
0.02 and in white matter from 0.18 +/- 0.03 to 0.30 +/- 0.03. There were
significant decreases in tortuosity in the dorsal horn and in the intermediate
region and decreases in non-specific uptake in the intermediate region
and in the ventral horn. Although the inflammatory reaction and the astrogliosis
preceded and greatly outlasted the neurological symptoms, the BBB damage
had a similar time course. Moreover, there was a close correlation between
the changes in extracellular space diffusion parameters and the manifestation
of neurological signs. We suggest that the expansion of the extracellular
space alters the diffusion properties in the spinal cord. This may affect
synaptic as well as non-synaptic transmission, intercellular communication
and recovery from acute EAE, and may contribute to the manifestation of
neurological signs in EAE rats.