Induced Spreading Depression Evokes Cell Division of Astrocytes in the Subpial Zone, Generating Neural Precursor-Like Cells and New Immature Neurons in the Adult Cerebral Cortex

Abstract

Background and Purpose-New immature neurons appear out of the germinative zone, in cortical Layers V to VI, after induced spreading depression in the adult rat brain. Because neural progenitors have been isolated in the cortex, we set out to determine whether a subgroup of mature cells in the adult cortex has the potential to divide and generate neural precursors. Methods-We examined the expression of endogenous markers of mitotic activity, proliferating cell nuclear antigen, and vimentin as a marker for neuronal progenitor cells, if any, in the adult rat cortex after spreading depression stimulation. Immunohistochemical analysis was also performed using antibodies for proliferating cell nuclear antigen, for vimentin, and for nestin. Nestin is a marker for activity dividing neural precursors. Results-At

Cortical Spreading Depression Closes Paravascular Space and Impairs Glymphatic Flow: Implications for Migraine Headache

“…The potential relationship between headache and the glymphatic system is also supported by evidence for inhibition of glymphatic clearance of solutes and metabolites from the brain parenchyma during prolonged wakefulness (Xie et al, 2013) and after traumatic brain injury (Plog et al, 2015), conditions associated with migraine headache. Sleep disturbances, especially insomnia, reliably precipitate headache (Kelman and Rains, 2005) and show a strong association with migraine chronification (Jennum and Jensen, 2002;Dodick et al, 2003;Rains and Poceta, 2006;Rains et al, 2008;Lateef et al, 2011), whereas posttraumatic headache fulfilling migraine criteria is the most frequent symptom after traumatic brain injury (Theeler et al, 2013;Lucas et al, 2014;Anderson et al, 2015).…”

“…Since previous studies (Iliff et al, 2012(Iliff et al, , 2013(Iliff et al, , 2014) have largely dealt with penetrating vasculature, as opposed to surface vasculature, we also imaged the PVS in penetrating arteries. Closure of the PVS was also apparent around penetrating arteries (Fig.…”

“…Based on our findings, it may be worthwhile to determine whether partial closure of the PVS plays any role in the inhibition of glymphatic flow during prolonged wakefulness or after traumatic brain injury. In this case, accumulation of interstitial waste, which may occur during sleep deprivation (Xie et al, 2013), may lower the threshold for migraine onset, whereas enhanced glymphatic clearance of solutes from the brain during sleep (Xie et al, 2013) may partially explain the mechanisms by which sleep terminates migraine.…”

“…The glymphatic system is a newly characterized series of extracellular compartments that clears waste from the brain parenchyma (Carare et al, 2008;Jessen et al, 2015) into paravascular spaces (PVSs) and then through the dural lymphatics to cervical lymph nodes (Aspelund et al, 2015;Louveau et al, 2015). Impairment of glymphatic pathway function in the aging brain (Kress et al, 2014), during prolonged wakefulness (Xie et al, 2013), after traumatic brain injury (Iliff et al, 2014), or in aquaporin 4 (AQP4) knock-out mice (Iliff et al, 2012) suggests that proper clearance of interstitial fluid and solutes, such as amyloid-␤ and hyperphosphorylated tau, through this paravascular drainage system is critical for maintaining a healthy brain.…”

Thinning, movement, and volume loss of residual cortical tissue occurs after stroke in the adult rat as identified by histological and magnetic resonance imaging analysis

“…Another possible cellular change is the birth, migration, and maturation of new neurons (Abrahams, 2009;Keiner et al, 2009;Kuge et al, 2009;Wurm, et al, 2007;Xue et al, 2009;Zhao et al, 2009). By co-labeling cells with BrdU and NeuN, it has been suggested that neural progenitor cells might migrate from the dentate gyrus and subventricular zone into the overlying ischemic cortex.…”