Ovariectomy in the developing rat decelerates cortical spreading depression in adult brain

Abstract

The brain of mammals is one important target organ for the action of gonadal steroids and, when occurring during development, this hormonal influence may result in important repercussion on the brain electrophysiological properties at adulthood, some of which depending on the brain excitability. Here we have characterized in early-ovariectomized adult rats the brain ability to propagate the excitability-related phenomenon known as cortical spreading depression (CSD), as an index of the cerebral electrophysiological effects of the early-induced absence of the ovarian hormones. Wistar female rat pups (7-day old) underwent bilateral ovariectomy (Ovx group; n=21) or Sham surgery (Sham group; n=22), or no surgery (Naive group; n=22). When the pups became adult (90-130 days), they were submitted to the recording of CSD (electrocorticogram and slow DC-voltage variation) in two points of the cortical surface during 4h. Compared with both Naïve and Sham controls, bilateral ovariectomy early in life resulted in significantly higher body weights (from days 50-65 onwards) and severely reduced uterus weights at adulthood. Furthermore, in the Ovx animals the amplitudes and durations of the DC-potential changes of CSD were higher, and the CSD propagation velocities were reduced. Another group of rats ovariectomized in adulthood did not present such CSD alterations. It is concluded that ovariectomy during brain development is causally associated with the CSD changes in the adult brain, indicating a long-lasting effect, which we suggest as being related to the long-term suppression of the action of the ovarian hormones on brain excitability.

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

“…In the present work, we observed a non‐significant trend ( P = 0.061) for interactions between treadmill exercise and MSG treatment on the susceptibility of the brain to CSD and microglial reaction in the cerebral cortex. Because of recent evidence suggesting the influence of ovarian hormones on CSD propagation (Accioly et al, 2012), we decided to use only male rats.…”

“…When the animals were 45-60 days old they were submitted to CSD recording for 4 h as described previously (Accioly et al, 2012). Under anesthesia (1 g/kg urethane plus 40 mg/kg chloralose, ip), the rat's head was secured in a stereotaxic apparatus (Kopf, USA) and three trephine holes (2-3 mm in diameter) drilled in the right side of the skull: two holes in the parietal bone and one in the frontal bone, aligned in the anteroposterior direction and parallel to the midline.…”

17-β-Estradiol induces spreading depression and pain behavior in alert female rats

“…SD events were determined by the DC shifts that were calculated from both the frontal and parietal electrodes that recorded the shifts. Cortical activity was defined as depressed during these events by measuring the significant reductions in both the power and amplitude of the dEEG tracings (i.e., recorded electrical activity was only considered an SD event when in both frontal and parietal electrodes: 1) the AC current was reduced by half; 2) the DC current exhibited a downward shift by a minimum of 1mV; and 3) for a minimal duration of 30 s [ 12 , 41 , 42 , 44 , 50 ]; Figure 1C ). The velocity of SD propagation was determined by analyzing the difference in time of onset of DC current depression between the frontal and parietal electrodes and dividing into 4mm (the distance between the two electrodes).…”

“…Non-invasive epidural EEGs have been used to determine brain activity in rats since 1979 [ 12 , 38 – 41 ]. Over time, the implantation technique has been substantially improved upon to yield highly reproducible and stable recordings [ 12 , 41 ] with successful epidural EEG recordings of CSD events by a number of groups in the context of migraine [ 42 – 44 ]. SD events in humans can be detected with traditional EEG leads on the cortical surface [ 45 ] or using scalp AC-EEG [ 46 ] intracortical and subdural recordings are only obtained during procedures with patients requiring intracranial pressure relief (i.e., TBI) or tissue removal [ 47 – 50 ].…”

Valeriana officinalis Counteracts Rotenone Effects on Spreading Depression in the Rat Brain in vivo and Protects Against Rotenone Cytotoxicity Toward Rat Glioma C6 Cells in vitro

“…Moreover, the combined administration of valerian plus rotenone in the same animal showed that valerian has the ability to protect the brain against the CSD velocity alterations induced by rotenone. Because ovarian hormones seem to influence CSD (Accioly et al, 2012;Accioly and Guedes, 2017), we decided to use only male rats.…”