Ascorbic Acid Prevents Blood–Brain Barrier Disruption and Sensory Deficit Caused by Sustained Compression of Primary Somatosensory Cortex

Abstract

Transient compression of rat somatosensory cortex has been reported to affect cerebral microvasculature and sensory function simultaneously. However, the effects of long-term cortical compression remain unknown. Here, we investigated whether and to what extent sustained but moderate epidural compression of rat somatosensory cortex impairs somatic sensation and/or cortical microvasculature. Electrophysiological and behavioral tests revealed that sustained compression caused only short-term sensory deficit, particularly at 1 day after injury. Although the diameter of cortical microvessels was coincidentally reduced, no ischemic insult was observed. By measuring Evans Blue and immunoglobulin G extravasation, the blood-brain barrier (BBB) permeability was found to dramatically increase during 1 to 3 days, but this did not lead to brain edema. Furthermore, immunoblotting showed that the BBB component proteins occludin, claudin-5, type IV collagen, and glial fibrillary acidic protein were markedly upregulated in the injured cortex during 1 to 2 weeks when BBB regained integrity. Conversely, treatment of ascorbic acid prevented compression-induced BBB disruption and sensory impairment. Together, these data suggest that sustained compression of the somatosensory cortex compromises BBB integrity and somatic sensation only in the early period. Ascorbic acid may be used therapeutically to modulate cortical compression and/or BBB dysfunction.

Effects of epidural compression on stellate neurons and thalamocortical afferent fibers in the rat primary somatosensory cortex

“…We analyzed the TCA fiber density in individual barrels and found that compared to the sham group, the TCA fiber density abruptly increased at 1 day post-compression, irrespective of the staining method ( Figs 7A, 7B, 7J, and 7K). The rapid increase of TCA fiber density is likely due to the abrupt decrease of cortical layer thickness caused by epidural compression as shown in previous studies (Chen et al 2003, Lin et al 2010) and the little if any loss of TCA fibers at this time point. However, it is noteworthy that compared to the findings at 1 day post-compression ( Fig.…”

“…Compared to sham-operation ( Figs 5A and 5E), sustained epidural compression for 1 week remarkably increased both 3-NT and 4-HNE expressions by approximately 125% and 51%, respectively (P<0.01) in the barrel field (Figs 5B, 5F, and 5I). Notably, there is also an increase of 3-NT and 4-HNE expressions at 1 day post-compression as shown previously (Lin et al 2010). We further examined whether antioxidants could block the oxidative stress caused by epidural compression.…”

“…The diameter of cortical microvessels is only transiently and slightly reduced (Lin et al 2010). Brain edema (Lin et al 2010) and microglial activation (Chen et al 2003) were not seen after epidural compression. Thus, our current study could focus on the plasticity of stellate neurons and TCA fibers in response to only physical compression which was not complicated with ischemia, cell death, brain edema, or microglial activation.…”

“…These reactive oxygen species (ROS; e.g., O 2 -and OH -) and reactive nitrogen species (RNS; e.g., NO and ONOO -) can cause lipid peroxidation (Zhang et al 1999), protein nitration (Beckman and Koppenol 1996), and DNA damage (Mendez et al 2004). Our earlier study has shown that treatment of NADPH oxidase inhibitor apocynin or antioxidant ascorbic acid prevents the reduction of somatosensory evoked potential (SSEP) amplitude caused by sustained epidural compression (Lin et al 2010). These results suggest that oxidative stress may be involved in the pathological alterations of somatosensory cortex caused by compression.…”

An Overview of the Characteristics and Function of Vitamin C in Various Tissues: Relying on its Antioxidant Function

“…High doses of ascorbate (1 g/kg) blocked dopamine mediated circling behavior, something that may also be achieved through dopamine receptor blockers [1];ascorbate inhibit binding of specific D 1 and D 2 receptors [13]. Recently, it has been reported that treatment with vitamin C prevents compression-induced blood-brain barrier (BBB) disruption and both low and high vitamin C levels have an impact on the number and size of mitochondria [53], as BBB disruption and mitochondrial dysfunction are well-known risk factors for oxidative stress and Alzheimer disease pathogenesis [54].…”