Abstract
The present study was undertaken to examine the effects of methylprednisolone on the expression and activity of calpain in spinal cord tissue following spinal cord ischemia-reperfusion injury in rats. Adult male Sprague-Dawley rats were subjected to sham operations, ischemia-reperfusion and vehicle treated, or ischemia-reperfusion with methylprednisolone administration after injury. The expression of calpain I in the injured segments of the spinal cord as well as the degradation of the 68 kD neurofilament protein (NFP), a calpain-specific substrate, was determined at 3 h, 24 h, 72 h and 7 days after reperfusion using immunohistochemical labeling and western blot analysis, respectively. Three hours after spinal cord reperfusion, calpain I-positive cells and NFP degradation products were evident. The number of positive cells and immunoreactivity increased with time and peaked at 72 h after reperfusion. In addition, the number of calpain I-positive cells and the abundance of NFP degradation products were significantly lower in the methylprednisolone group, compared with vehicle treated animals following ischemia-reperfusion injury. The results of this study suggest that methylprednisolone can inhibit the expression and degradation activity of calpain following ischemia-reperfusion injury, providing further insight into the therapeutic benefits of methylprednisolone treatment for spinal cord injury.
Highlights
Glutamate (Glu) is the major excitatory neurotransmitter in the mammalian CNS and approximately half of all neurons in the brain are classified as glutamatergic [1]
We have previously demonstrated that chronic exposure to low doses of domoic acid (DOM; a selective KA receptors (KAR) agonist) during a critical period of brain development produces adult animals that demonstrate social withdrawal [12], deficient pre-pulse inhibition (PPI) [13] and latent inhibition (LI) [14], and increases in respon- siveness to novelty [15], which may arguably reflect negative, cognitive, and positive symptoms of schizo- phrenia, respectively
Prefrontal Cortex An analysis of immunoreactivity in the right medial prefrontal cortex (mPFC) of male rats revealed a statistically significant treatment effect with DOM-treated rats exhibiting less tyrosine hydroxylase (TH) staining than SAL-treated counterparts [t(9) = −2.392, p = 0.02] (Figure 2(b)), an effect not present in female DOMtreated rats (Figure 2(a))
Summary
Glutamate (Glu) is the major excitatory neurotransmitter in the mammalian CNS and approximately half of all neurons in the brain are classified as glutamatergic [1]. We have previously demonstrated that chronic exposure to low doses of domoic acid (DOM; a selective KAR agonist) during a critical period of brain development produces adult animals that demonstrate social withdrawal [12], deficient pre-pulse inhibition (PPI) [13] and latent inhibition (LI) [14], and increases in respon- siveness to novelty [15], which may arguably reflect negative, cognitive, and positive symptoms of schizo- phrenia, respectively These observations, in conjunction with additional previously published data from our labo- ratory suggesting that early postnatal exposure to low-doses of DOM produce alterations in the functional in- tegrity of the mesocorticolimbic pathway [15,16,17] and altered cognitive functioning [17], are largely consistent with both clinical manifestations of schizophrenia and with those changes reported in existing animal models [18,19,20,21,22]
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