Abstract P730: MCA Stroke Chronically Disrupts Hippocampal Activity and Cortico-Hippocampal Communication

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Zachary Ip ◽  
Gratianne Rabiller ◽  
Jiwei He ◽  
Shivalika Chavan ◽  
Yasuo Nishijima ◽  
...  

Introduction: Cognition and memory deficits are common sequelae following middle cerebral artery (MCA) stroke, one of the most common strokes in humans. However MCA stroke does not compromise the structural integrity of the hippocampus, which is highly involved in memory function, because the MCA does not supply blood flow to the hippocampus. We previously reported on the acute effect of MCA stroke, where we observed increased hippocampal activity and cortico-hippocampal communication. Here we investigate chronic changes to local oscillations and cortico-hippocampal communication following MCA occlusion in rats two weeks and one month following stroke. Hypothesis: Cortical stroke affects remote brain regions, disrupting hippocampal function and cortico-hippocampal communication. Methods: We subjected male rats (n=28) to distal MCA occlusion compared to controls (n=19). We recorded local field potentials simultaneously from cortex and hippocampus two weeks and one month following stroke using 16-site linear electrode arrays under urethane anesthesia. We analyzed signal power, brain state, CFC, and sharp wave SPW-Rs to assess hippocampal function and cortico-hippocampal communication. Results: Our results show disruptions to local oscillations; lowered delta (1-3 Hz) signal power in the cortex and hippocampus, increased signal power in gamma (30-60 Hz) and high gamma (60-200 Hz) in cortex and hippocampus. Theta/delta brain state is disrupted, and SPW-Rs increase in power at two weeks, before returning to baseline levels at one month. Communication is also disrupted; Theta-gamma coupling, a measure of information being communicated between regions, breaks down after stroke. Conclusions: These results suggest that chronic stroke causes significant changes to hippocampal function, which can be characterized by these electrophysiological biomarkers, establishing putative targets for targeted stimulation therapies.

2019 ◽  
Author(s):  
Jamie N. Krueger ◽  
Jacob H. Wilmot ◽  
Yusuke Teratani-Ota ◽  
Kyle R. Puhger ◽  
Sonya E. Nemes ◽  
...  

AbstractThe current study determined if inactivation of the dorsal hippocampus impairs the retrieval of newly formed context fear memories. This region was silencing by activating inhibitory neurons or by hyperpolarizing pyramidal cells directly. When inhibitory neurons were stimulated with ChR2, memory retrieval was significantly impaired. In contrast, when the same neurons were activated with the excitatory DREADD hM3Dq, retrieval was not affected. This dissociation was not due to differences in inhibition, as both manipulations activated interneurons and reduced excitation throughout the dorsal hippocampus. Therefore, we hypothesize that the retrieval deficit caused by ChR2 stimulation is due to an immediate reduction in hippocampal activity that does not provide enough time for other brain regions to compensate. Stimulation of DREADDs, on the other hand, produces a gradual loss of excitation that takes several minutes to reach asymptote. This appears to be a sufficient amount of time for extra-hippocampal structures to become engaged and express context fear. Implications for theories of hippocampal function, systems consolidation and memory retrieval are discussed.


2020 ◽  
Vol 15 ◽  
Author(s):  
Samar R. Saleh ◽  
Mariam M. Abady ◽  
Mohammed Nofal ◽  
Nashwa W. Yassa ◽  
Mohamed S. Abdel-latif ◽  
...  

Background: Berberine (BBR), an isoquinoline alkaloid, acts as a multipotent active pharmaceutical ingredient to counteract several types of dementia based on its numerous pharmacological actions including antioxidant, antiinflammatory, cholesterol-lowering effect, and inhibition of Aβ production and AChE. However, BBR suffers from poor absorption, bioavailability and brain drug uptake. The present study is directed for the formulation and characterization of Chitosan BBR-nanoparticles (BBR-NPs) as well as the estimation of its neuroprotective effects against scopolamine induced cognitive impairments. Methods: BBR-NPs were formulated using ionic gelation method and tripolyphosphate was chosen as a cross linker. Nanoparticles size, zeta potential, encapsulation efficiency and releasing profile were estimated. To investigate the neuroprotective effects, adult fifty six Wistar male rats were randomly distributed into: three control groups, received saline, polyethylene glycol or chitosan- NPs respectively; induced group, received scopolamine (2 mg/ kg, i.p.) and three treated groups were orally administrated BBR (50 mg/ kg), BBR- NP (7 mg/ kg) and donepezil (2.25 mg/ kg, as positive control) followed by scopolamine injection after 40 min, daily for 4 weeks. Morris water maze test, oxidative stress parameters, cholinergic and amyloid-β processing intermediates as well as neuroplasticity markers and histopathological examination were assessed. Results: Our results showed that BBR- NPs were better than BBR and donepezil as BBR- NPs were powerful inhibitory ligands toward AChE and Aβ42 formation and significantly down regulated Tau, iNOS and BACE gene expression in rats’ hippocampus. BBR-NPs administration, at 1/6 of BBR therapeutic recommended dose, significantly improved learning and memory function. This could be accredited to the diminution of oxidative stress and amyloid-β toxicity in addition to the improvement of the neuroplasticity markers. Conclusions: The enhancing effect of BBR- NPs could be related to the enhancing of its bioavailability, absorption and brain drug uptake which need more investigation in future work.


2005 ◽  
Vol 24 (6) ◽  
pp. 451-467 ◽  
Author(s):  
Raymond G. York ◽  
John Barnett ◽  
Michael F. Girard ◽  
David R. Mattie ◽  
Marni V. K. Bekkedal ◽  
...  

A developmental neurotoxicity study was conducted to generate additional data on the potential functional and morphological hazard to the central nervous system caused by ammonium perchlorate in offspring from in utero and lactation exposure. Female Sprague-Dawley rats (23 to 25/group) were given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 10.0 mg/kg-day perchlorate in the drinking water beginning 2 weeks prior to mating and continuing through day 10 of lactation for the behavioral function assessment or given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 30.0 mg/kg-day beginning on gestation day 0 and continuing through day 10 of lactation for neurodevelopment assessments. Motor activity was conducted on postpartum days 14, 18, and 22 and juvenile brain weights, neurohistopathological examinations, and regional brain morphometry were conducted on postpartum days 10 and 22. This research revealed a sexually dimorphic response, with some brain regions being larger in perchlorate-treated male rats than in comparable controls. Even so, there was no evidence of any obvious exposure-related effects on male rat brain weights or neuropathology. The most consistent exposure-related effect in the male pups was on the thickness of the corpus callosum, with both the right- and left-sided measures of the thickness of this white matter tract being significantly greater for the male pups in the 0.1 and 1.0 mg/kg-day exposure groups. The behavioral testing suggests prenatal exposure to ammonium perchlorate does not affect the development of gross motor movements in the pups.


2020 ◽  
Vol 21 (12) ◽  
pp. 4503
Author(s):  
Sabah Nisar ◽  
Ajaz A. Bhat ◽  
Sheema Hashem ◽  
Najeeb Syed ◽  
Santosh K. Yadav ◽  
...  

Post-traumatic stress disorder (PTSD) is a highly disabling condition, increasingly recognized as both a disorder of mental health and social burden, but also as an anxiety disorder characterized by fear, stress, and negative alterations in mood. PTSD is associated with structural, metabolic, and molecular changes in several brain regions and the neural circuitry. Brain areas implicated in the traumatic stress response include the amygdala, hippocampus, and prefrontal cortex, which play an essential role in memory function. Abnormalities in these brain areas are hypothesized to underlie symptoms of PTSD and other stress-related psychiatric disorders. Conventional methods of studying PTSD have proven to be insufficient for diagnosis, measurement of treatment efficacy, and monitoring disease progression, and currently, there is no diagnostic biomarker available for PTSD. A deep understanding of cutting-edge neuroimaging genetic approaches is necessary for the development of novel therapeutics and biomarkers to better diagnose and treat the disorder. A current goal is to understand the gene pathways that are associated with PTSD, and how those genes act on the fear/stress circuitry to mediate risk vs. resilience for PTSD. This review article explains the rationale and practical utility of neuroimaging genetics in PTSD and how the resulting information can aid the diagnosis and clinical management of patients with PTSD.


2016 ◽  
Vol 20 (2) ◽  
pp. 191-197
Author(s):  
D. I. Peregud ◽  
S. V. Freiman ◽  
A. O. Tishkina ◽  
L. S. Sokhranyaeva ◽  
N. A. Lazareva ◽  
...  
Keyword(s):  

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Blaise Robert ◽  
Eyal Y Kimchi ◽  
Yurika Watanabe ◽  
Tatenda Chakoma ◽  
Miao Jing ◽  
...  

Basal forebrain cholinergic neurons (BFCNs) project throughout the cortex to regulate arousal, stimulus salience, plasticity, and learning. Although often treated as a monolithic structure, the basal forebrain features distinct connectivity along its rostrocaudal axis that could impart regional differences in BFCN processing. Here, we performed simultaneous bulk calcium imaging from rostral and caudal BFCNs over a one-month period of variable reinforcement learning in mice. BFCNs in both regions showed equivalently weak responses to unconditioned visual stimuli and anticipated rewards. Rostral BFCNs in the horizontal limb of the diagonal band were more responsive to reward omission, more accurately classified behavioral outcomes, and more closely tracked fluctuations in pupil-indexed global brain state. Caudal tail BFCNs in globus pallidus and substantia innominata were more responsive to unconditioned auditory stimuli, orofacial movements, aversive reinforcement, and showed robust associative plasticity for punishment-predicting cues. These results identify a functional topography that diversifies cholinergic modulatory signals broadcast to downstream brain regions.


eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Elizabeth D Kirby ◽  
Sandra E Muroy ◽  
Wayne G Sun ◽  
David Covarrubias ◽  
Megan J Leong ◽  
...  

Stress is a potent modulator of the mammalian brain. The highly conserved stress hormone response influences many brain regions, particularly the hippocampus, a region important for memory function. The effect of acute stress on the unique population of adult neural stem/progenitor cells (NPCs) that resides in the adult hippocampus is unclear. We found that acute stress increased hippocampal cell proliferation and astrocytic fibroblast growth factor 2 (FGF2) expression. The effect of acute stress occurred independent of basolateral amygdala neural input and was mimicked by treating isolated NPCs with conditioned media from corticosterone-treated primary astrocytes. Neutralization of FGF2 revealed that astrocyte-secreted FGF2 mediated stress-hormone-induced NPC proliferation. 2 weeks, but not 2 days, after acute stress, rats also showed enhanced fear extinction memory coincident with enhanced activation of newborn neurons. Our findings suggest a beneficial role for brief stress on the hippocampus and improve understanding of the adaptive capacity of the brain.


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