Increased calcium influx triggers and accelerates cortical spreading depression in vivo in male adult rats

Abstract

Cortical spreading depression (CSD) is a depolarization wave associated with neurological disorders such as migraine, cerebral ischemia and traumatic brain injury. The mechanism of action of this phenomenon still remains unclear. Although it is suggested that extracellular K(+) accumulation contributes to CSD, other ions may play a relevant role in the mechanism of propagation of the wave. In this context, we hypothesize that Ca(2+) may play an important function in the wave propagation. Our results demonstrate that enhancing Ca(2+) influx into the cells by topical cortical application of the ionophore A23187 (10 μM, 50 μM and 100 μM solutions) increases the velocity of CSD propagation in a dose-dependent manner, and a much higher dose of this compound (2 mM) triggers CSD. In conclusion, increased Ca(2+) influx can be a key element in the induction mechanism of the CSD, and should be assessed in further experimental strategies targeting brain disorders related to CSD.

Spreading depression features and Iba1 immunoreactivity in the cerebral cortex of developing rats submitted to treadmill exercise after treatment with monosodium glutamate

“…In this context, enhanced immunolabeling of the microglial cells with a monoclonal antibody against Iba1 could be interpreted as a specific cell reaction against imbalanced calcium influx. Interestingly, both glutamate receptor activation and transmembrane calcium flux alterations are known to influence CSD, as demonstrated by our laboratory (Guedes et al, 1988; Torrente et al, 2013) and others (Marrannes et al, 1988; Siesjö and Bengtsson, 1989).…”

Abnormal synaptic Ca2+ homeostasis and morphology in cortical neurons of familial hemiplegic migraine type 1 mutant mice

“…Consistent with its effect on excitability, resting [Ca 21 ] i also modulates CSD susceptibility. Increasing resting [Ca 21 ] i augments CSD propagation, 55 and conversely, 20% reduction in resting [Ca 21 ] i in tottering and leaner mice, which also carry Cacna1a mutations but with a loss of Ca V 2.1 function, is associated with diminished CSD susceptibility. 56,57 Here we show that inhibition of the Ca V 2.1 gain-of-function by the gating modifier BHQ FIGURE 5: Abnormal synaptic morphology in familial hemiplegic migraine type 1 mutants at resting state.…”

Cortical spreading depression and mitochondrial dysfunction with aging: lessons from ethanol abuse

“…Chronic ethanol administration affects the antioxidant defenses of the brain by reducing the levels of glutathione, peroxidase, α-tocopherol, glutathione reductase and catalase (Bezerra Rde et al, 2005), and the aged brain is particularly affected by this reduced antioxidant scavenging system (Reiter, 1995). Indeed, it is possible that cytoplasmic calcium levels may also be implicated in CSD deflagration (Torrente et al, 2014b). Altogether, these findings suggest that there are multiple mechanisms by which ethanol may damage the brain (Figure 1).…”