Madhuvika Murugan, Vijayalakshmi Santhakumar, Sridhar S. Kannurpatti
Abstract
Mild to moderate traumatic brain injury (mTBI) leads to secondary neuronal loss via excitotoxic mechanisms, including mitochondrial Ca(2+) overload. However, in the surviving cellular population, mitochondrial Ca(2+) influx, and oxidative metabolism are diminished leading to suboptimal neuronal circuit activity and poor prognosis. Hence we tested the impact of boosting neuronal electrical activity and oxidative metabolism by facilitating mitochondrial Ca(2+) uptake in a rat model of mTBI. In developing rats (P25-P26) sustaining an mTBI, we demonstrate post-traumatic changes in cerebral blood flow (CBF) in the sensorimotor cortex in response to whisker stimulation compared to sham using functional Laser Doppler Imaging (fLDI) at adulthood (P67-P73). Compared to sham, whisker stimulation-evoked positive CBF responses decreased while negative CBF responses increased in the mTBI animals. The spatiotemporal CBF changes representing underlying neuronal activity suggested profound changes to neurovascular activity after mTBI. Behavioral assessment of the same cohort of animals prior to fLDI showed that mTBI resulted in persistent contralateral sensorimotor behavioral deficit along with ipsilateral neuronal loss compared to sham. Treating mTBI rats with Kaempferol, a dietary flavonol compound that enhanced mitochondrial Ca(2+) uptake, eliminated the inter-hemispheric asymmetry in the whisker stimulation-induced positive CBF responses and the ipsilateral negative CBF responses otherwise observed in the untreated and vehicle-treated mTBI animals in adulthood. Kaempferol also improved somatosensory behavioral measures compared to untreated and vehicle treated mTBI animals without augmenting post-injury neuronal loss. The results indicate that reduced mitochondrial Ca(2+) uptake in the surviving populations affect post-traumatic neural activation leading to persistent behavioral deficits. Improvement in sensorimotor behavior and spatiotemporal neurovascular activity following kaempferol treatment suggests that facilitation of mitochondrial Ca(2+) uptake in the early window after injury may sustain optimal neural activity and metabolism and contribute to improved function of the surviving cellular populations after mTBI.
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 March 2016.
All research outputs
#14,840,844
of 22,854,458 outputs
Outputs from Frontiers in Systems Neuroscience
#891
of 1,344 outputs
Outputs of similar age
#168,295
of 299,380 outputs
Outputs of similar age from Frontiers in Systems Neuroscience
#30
of 36 outputs
Altmetric has tracked 22,854,458 research outputs across all sources so far. This one is in the 33rd percentile – i.e., 33% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,344 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.7. This one is in the 29th percentile – i.e., 29% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 299,380 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 40th percentile – i.e., 40% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 36 others from the same source and published within six weeks on either side of this one. This one is in the 16th percentile – i.e., 16% of its contemporaries scored the same or lower than it.
