Biology subjects

Karatas, H.

Publications and source records attributed to Karatas, H..

3 recordsLinked to original sources

bioRxiv2026

Mesoscale Functional Reorganization of Cortical Networks After Cortical Spreading Depression

BackgroundResting-state functional imaging is increasingly used to understand how cortical networks modulate and respond to pain. Awake imaging with a minimally invasive approach is key to observe the natural state of the brain. As migraine with aura, a common headache disorder, can be experimentally modeled by cortical spreading depressions (CSD) in rodents, it is essential to understand the impact of CSD on functional connectivity and network topology to find imaging cues of trigeminovascular activation and headache. MethodsWe used awake widefield intrinsic optical-signal imaging (IOSI) on optically cleared windows to non-invasively characterize the impact of CSDs on bihemispheric resting-state static and dynamic functional connectivity patterns and network topology. A subset of mice was chronically treated with amitriptyline to examine the effect of susceptibility to CSD on connectivity. After baseline imaging, CSD was triggered optogenetically and confirmed by laser speckle contrast imaging. A group of mice received intraperitoneal naproxen after CSD to suppress headache. IOSI was repeated at 30 minutes, 60 minutes, 4 hours, and 24 hours after CSD. The mouse grimace scale was scored at each time point for behavioral headache documentation. ResultsWe observed time-dependent changes in resting-state functional connectivity that were reversed by naproxen. Amitriptyline, a prophylactic migraine medication, decreased susceptibility to CSD and modified resting-state functional connectivity differently than controls. Network analysis with graph-theoretical methods revealed barrel and retrosplenial cortices as potential key players in trigeminal pain processing after CSD. Dynamic functional connectivity analysis demonstrated functional connectivity states, with fractional occupancy and mean dwell time of these states showing distinct CSD and pain-modulated states. A support vector machine was utilized to predict CSD-mediated dynamic connectivity changes in controls. ConclusionOur results bring insight into potentially headache-associated changes in resting-state cortical functional connectivity after CSD and how this functional reorganization is influenced by acute and chronic medications for migraine.

neuroscience↗

bioRxiv2024

Reduced Folate Carrier 1 (RFC1/Slc19a1) Suppression Exacerbates Blood-Brain Barrier Breakdown in Experimental Ischemic Stroke in Adult Mice

The Reduced Folate Carrier 1 (RFC1), also called solute carrier family 19 member 1 (SLC19A1/SLC19a1), is recognized for transporting folates across the blood-brain barrier (BBB). RFC1 has recently been defined as a hypoxia-immune related gene whose expression levels were induced by acute retinal ischemia, suggesting that RFC1 may have a role in the response of the brain to ischemic injury. Despite a recent human meta-analysis suggesting an association between certain RFC1 polymorphisms and the risk of silent brain infarctions, preclinical evidence concerning the potential role of RFC1 in acute ischemic stroke has yet to be presented. To investigate this, we first characterized RFC1 protein expression in mouse microvessels and pericytes which play significant roles in stroke pathophysiology. Then, we examined the temporal (1-h, 24-h, and 48-h) and spatial (infarct, periinfarct, contralateral) expression of RFC1 protein in the intraluminal transient middle cerebral artery occlusion mouse model. Finally, we knocked down RFC1 protein with RFC1-siRNA in the potential periinfarct region before induction of ischemia and investigated BBB integrity and infarct size in vivo via 7T-MRI. Moreover, we utilized a pharmacological modulation-methotrexate, a non-covalent inhibitor of RFC1- to further investigate the role of RFC1 in maintaining BBB integrity. Our study revealed that, i) RFC1 protein levels were dynamic throughout the acute phases of ischemic stroke, ii) RFC1 suppression aggravated the BBB leakage during ischemia. These results emphases the role of RFC1 in the pathophysiology of ischemic stroke and supports the evidence from human studies.

neuroscience↗

bioRxiv2022

The Effect of P2X7 Antagonism on Subcortical Spread of Optogenetically-Triggered Cortical Spreading Depression and Neuroinflammation

Migraine is a neurological disorder characterized by episodes of severe headache. Cortical spreading depression (CSD), the electrophysiological equivalent of migraine aura, results in opening of pannexin-1 megachannels that release ATP and triggers parenchymal neuroinflammatory signaling cascade in the cortex. Migraine symptoms suggesting subcortical dysfunction bring subcortical spread of CSD under the light. Here, we investigated the role of purinergic P2X7 receptors on the subcortical spread of CSD and its consequent neuroinflammation using a potent and selective P2X7 antagonist, JNJ-47965567. P2X7 antagonism had no effect on the CSD threshold and characteristics but increased the latency to hypothalamic voltage deflection following CSD showing that ATP acts as a mediator in the subcortical spread. P2X7 antagonism also prevented hypothalamic neuronal activation following CSD, revealed by bilateral decrease in hypothalamic c-fos positive neuron count. P2X7 antagonism further stopped the CSD-induced neuroinflammation revealed by decreased nuclear translocation of NF-kappa B-p65 in astrocytes and decreased HMGB1 release. Following CSD we observed an increase in neuronal cytoplasmic P2X7R signal in cortex and subcortical structures (thalamus, hypothalamus, striatum, hippocampus) concordant with the neuroinflammation which is also prevented by P2X7R antagonism. In conclusion, our data suggest that P2X7R plays an imperative role in CSD-induced neuroinflammation, subcortical spread of CSD and CSD-induced hypothalamic neuronal activation hence can be a potential target in migraine treatment.

neuroscience↗