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

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.

Aging-dependent brain electrophysiological effects in rats after distinct lactation conditions, and treadmill exercise: a spreading depression analysis.

Aging-related neurophysiological alterations are a matter of growing concern in gerontology. Physical exercise has been therapeutically employed to ameliorate aging-associated deleterious neurological changes. The aging process, as well as the effects of treadmill exercise on brain excitability, can be influenced by nutritional demands during lactation. In this study we investigated whether physical exercise, lactation conditions, and aging interact and modulate brain electrophysiology as indexed by the excitability-related phenomenon known as cortical spreading depression (CSD). Wistar male rats were suckled in litters of 12 or 6 pups (constituting two groups named L12 and L6), with different lactation conditions. Each group was subdivided into exercised (treadmill) and sedentary. CSD was recorded immediately after the exercise period for young, adult, and aged groups (respectively 45-60, 120-130, and 600-700 days old). In L6 groups, the mean CSD velocity (in mm/min) ranged from 2.57±0.24 in aged rats to 3.67±0.13 in young rats, indicating an aging-related CSD deceleration. The L12 condition accelerated CSD (velocities ranging from 3.11±0.21 to 4.35±0.16 in aged and young rats, respectively) while treadmill exercise decelerated it in both L6 groups (range: 3.02±0.19 to 2.57±0.24) and L12 groups (3.32±0.16 to 3.11±0.21), with an observed interaction between factors in the aged group. Furthermore, aging led to a significant failure of CSD propagation. These results contribute to the understanding of underlying mechanisms by which exercise and aging influence brain electrophysiological functioning, previously associated with distinct lactation conditions during the period of brain development.