scholarly journals Intraarterial anti-leptin therapy via ICA protects ipsilateral CA1 neurons subjected to ischemia and reperfusion

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0261644
Author(s):  
Amit Benbenishty ◽  
Jacob Schneiderman
Keyword(s):  
Carotid Artery ◽  
Common Carotid Artery ◽  
Right Hemisphere ◽  
Pyramidal Cells ◽  
Ca1 Neurons ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1 ◽  
The Right ◽  
Apoptosis And Necrosis

Background Brain reperfusion following an ischemic event is essential for tissue viability, however, it also involves processes that promote neuronal cell death. We have recently shown that local expression of the hormone leptin in cardiovascular organs drives deleterious remodeling. As cerebral ischemia-reperfusion (IR) lesions derive expression of both the leptin hormone and its receptor, we hypothesized that blocking leptin activity in the injured brain area will reduce the deleterious effects of IR injury. Methods C57BL6 male mice underwent bilateral common carotid artery and external carotid artery ligation. The right hemisphere was reperfused after 12 minutes, followed by intraarterial injection of either a low-dose leptin antagonist or saline solution via the ipsilateral ICA. The left common carotid artery remained ligated. Fifteen IR/leptin antagonist-injected and fourteen IR/saline-injected mice completed the experiment. Five days after surgery brains were collected and samples of the hippocampal CA1 region were analyzed for cell viability (H&E) and apoptosis (TUNEL and caspase3), for neuroinflammation (Iba1), and for signaling pathways of pSTAT3 and pSmad2. Results The right hemisphere hippocampal CA1 region subjected to IR and saline injection exhibited increased apoptosis and necrosis of pyramidal cells. Also, increased density of activated microglia/macrophages was evident around the CA1 region. Comparatively, leptin antagonist treatment at reperfusion reduced apoptosis and necrosis of pyramidal cells, as indicated by increased number of viable cells (p < 0.01), and reduced TUNEL (p < 0.001) and caspase3-positive cells (p<0.05). Furthermore, this treatment reduced the density of activated microglia/macrophages (p < 0.001) in the CA1 region. Signaling pathway analysis revealed that while pSTAT3 and pSmad2-positive cells were found surrounding the stratum pyramidal in saline-treated animals, pSTAT3 signal was undetected and pSmad2 was greatly reduced in this territory following leptin antagonist treatment (p < 0.01). Conclusions Inhibition of leptin activity in hemispheric IR injury preserved the viability of ipsilateral hippocampal CA1 neurons, likely by preventing apoptosis and local inflammation. These results indicate that intraarterial anti-leptin therapy may have clinical potential in reducing hemispheric brain IR injury.

scholarly journals Stroke as the Sole Manifestation of Takayasu Arteritis in a 15-Year-Old Boy with Latent Tuberculosis

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Espen Benjaminsen ◽  
Anne Reigstad ◽  
Vanja Cengija ◽  
Vibke Lilleby ◽  
Maria Carlsson
Keyword(s):  
Carotid Artery ◽  
Takayasu Arteritis ◽  
Common Carotid Artery ◽  
Right Hemisphere ◽  
Latent Tuberculosis ◽  
C Reactive Protein ◽  
Laboratory Findings ◽  
Case Presentation ◽  
Reactive Protein ◽  
The Right

Introduction. Takayasu arteritis is a rare disease affecting the aorta and its main branches, causing arterial claudication and end-organ ischemia, including stroke. The etiology is unknown but is believed to be autoimmune. An association between Takayasu arteritis and tuberculosis has been suggested, but the possible relation is unclear.Case Presentation. A 15-year-old Somali boy was diagnosed with latent tuberculosis. He had a lesion in the right lung, and both the tuberculin skin test by the Mantoux method and Quantiferon GOLD test turned out positive. After he suffered a cerebral infarct in the right hemisphere, childhood Takayasu arteritis was diagnosed. The diagnosis was based on diagnostic imaging showing a high-grade stenosis of the origin of the right common carotid artery, an occluded common carotid artery on the left side, a circumferential thickening of the vessel walls in the right and left common carotid artery, and laboratory findings with elevated C-reactive protein.Conclusion. Takayasu arteritis is an uncommon cause of stroke. It should however be kept in mind as a cause of cerebrovascular disease, especially in the young.

scholarly journals Stratum Lacunosum-moleculare Interneurons of the Hippocampus Coordinate Memory Encoding and Retrieval

2021 ◽  
Author(s):  
Jun Guo ◽  
Heankel Cantu Oliveros ◽  
So Jung Oh ◽  
Bo Liang ◽  
Ying Li ◽  
...  
Keyword(s):  
Pyramidal Cells ◽  
Brain Regions ◽  
Cellular Level ◽  
Memory Encoding ◽  
Ca1 Pyramidal Cells ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1 ◽  
Stratum Lacunosum Moleculare ◽  
Encoding And Retrieval

Encoding and retrieval of memory are two processes serving distinct biological purposes but operating in highly overlapping brain circuits. It is unclear how the two processes are coordinated in the same brain regions, especially in the hippocampal CA1 region where the two processes converge at the cellular level. Here we find that the neuron-derived neurotrophic factor (NDNF)-positive interneurons at stratum lacunosum-moleculare (SLM) in CA1 play opposite roles in memory encoding and retrieval. These interneurons show high activities in learning and low activities in recall. Increasing their activity facilitates learning but impairs recall. They inhibit the entorhinal- but dis-inhibit the CA3- inputs to CA1 pyramidal cells and thereby either suppress or elevate CA1 pyramidal cells′ activity depending on animal′s behavioral states. Thus, by coordinating entorhinal- and CA3- dual inputs to CA1, these SLM interneurons are key to switching the hippocampus between encoding and retrieval modes.

Na+/Ca2+ exchanger 1 alters in pyramidal cells and expresses in astrocytes of the gerbil hippocampal CA1 region after ischemia

2006 ◽  
Vol 1086 (1) ◽  
pp. 181-190 ◽  
Author(s):  
In Koo Hwang ◽  
Ki-Yeon Yoo ◽  
Dae Won Kim ◽  
Tae-Cheon Kang ◽  
Soo Young Choi ◽  
...  
Keyword(s):  
Pyramidal Cells ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1

scholarly journals Protective Effect of a Prosaposin-Derived, 18-Mer Peptide on Slowly Progressive Neuronal Degeneration after Brief Ischemia

2001 ◽  
Vol 21 (11) ◽  
pp. 1295-1302 ◽  
Author(s):  
Fumio Morita ◽  
Tong-Chun Wen ◽  
Junya Tanaka ◽  
Ryuji Hata ◽  
Junzo Desaki ◽  
...  
Keyword(s):  
Neuronal Degeneration ◽  
Neuronal Damage ◽  
Avoidance Task ◽  
Ca1 Neurons ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1 Neurons ◽  
Saposin C ◽  
Hippocampal Ca1

Slowly progressive degeneration of the hippocampal CA1 neurons was induced by 3-minute transient global ischemia in gerbils. Sustained degeneration of hippocampal CA1 neurons was evident 1 month after ischemia. To investigate the effects of an 18-mer peptide comprising the hydrophilic sequence of the rat saposin C domain (18MP) on this sustained neuronal degeneration, an intracerebroventricular 18MP infusion was initiated 3 days after ischemia. Histopathologic and behavior evaluations were conducted 1 week and 1 month after induction of ischemia. When compared with the vehicle infusion, 18MP treatment significantly increased the response latency time in a passive avoidance task. Increased neuronal density was also evident, as was the number of intact synapses in the hippocampal CA1 region at 1 week and 1 month after ischemia. 18MP treatment also significantly decreased the number of TUNEL-positive CA1 neurons 1 week after ischemia. Subsequent in vitro experiments using cultured neurons demonstrated that the 18MP at optimal extracellular concentrations of 1 to 100 fg/mL prevented nitric oxide–induced neuronal damage as expected and significantly up-regulated the expressions of bcl-xL mRNA and its translated protein. These results suggest that the gerbil model of 3-minute ischemia is useful in studying the pathogenesis of slowly progressive neuronal degeneration after stroke and in evaluating effects of novel therapeutic agents. It is likely that the 18MP at low extracellular concentrations prevents neuronal apoptosis possibly through up-regulation of the mitochondrial antiapoptotic factor Bcl-xL.

scholarly journals Translating the immediate effects of S-Ketamine using hippocampal subfield analysis in healthy subjects-results of a randomized controlled trial

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Höflich ◽  
Christoph Kraus ◽  
Ruth M. Pfeiffer ◽  
Rene Seiger ◽  
Dan Rujescu ◽  
...  
Keyword(s):  
Animal Models ◽  
Controlled Trial ◽  
Double Blind ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1 ◽  
Magnetic Resonance Imaging Mri ◽  
The Right ◽  
Mri Study ◽  
Post Hoc

AbstractAntidepressant doses of ketamine rapidly facilitate synaptic plasticity and modify neuronal function within prefrontal and hippocampal circuits. However, most studies have demonstrated these effects in animal models and translational studies in humans are scarce. A recent animal study showed that ketamine restored dendritic spines in the hippocampal CA1 region within 1 h of administration. To translate these results to humans, this randomized, double-blind, placebo-controlled, crossover magnetic resonance imaging (MRI) study assessed ketamine’s rapid neuroplastic effects on hippocampal subfield measurements in healthy volunteers. S-Ketamine vs. placebo data were analyzed, and data were also grouped by brain-derived neurotrophic factor (BDNF) genotype. Linear mixed models showed that overall hippocampal subfield volumes were significantly larger (p = 0.009) post ketamine than post placebo (LS means difference=0.008, standard error=0.003). Post-hoc tests did not attribute effects to specific subfields (all p > 0.05). Trend-wise volumetric increases were observed within the left hippocampal CA1 region (p = 0.076), and trend-wise volumetric reductions were obtained in the right hippocampal—amygdaloid transition region (HATA) (p = 0.067). Neither genotype nor a genotype–drug interaction significantly affected the results (all p > 0.7). The study provides evidence that ketamine has short-term effects on hippocampal subfield volumes in humans. The results translate previous findings from animal models of depression showing that ketamine has pro-neuroplastic effects on hippocampal structures and underscore the importance of the hippocampus as a key region in ketamine’s mechanism of action.

Changes in the Calcium Dependence of Glutamate Transmission in the Hippocampal CA1 Region After Brief Hypoxia-Hypoglycemia

1999 ◽  
Vol 82 (3) ◽  
pp. 1147-1155 ◽  
Author(s):  
A. Ouanonou ◽  
Y. Zhang ◽  
L. Zhang
Keyword(s):  
Calcium Influx ◽  
Brain Slices ◽  
Ca1 Neurons ◽  
Synaptic Potentials ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1 ◽  
Glutamate Transmission ◽  
Intracellular Ca ◽  
Dependent Processes

Using the model of hypoxia-hypoglycemia (HH) in rat brain slices, we asked whether glutamate transmission is altered following a brief HH episode. The HH challenge was conducted by exposing slices to a glucose-free medium aerated with 95% N2-5% CO2, for ∼4 min, and glutamate transmission in the hippocampal CA1 region was monitored at different post HH times. In slices examined ≤8 h post HH, CA1 synaptic field potentials are comparable in amplitude to controls, but are less sensitive to experimental manipulations designed to attenuate intracellular Ca2+ signals, as compared with controls. Reducing calcium influx, by applying a nonspecific calcium channel blocker Co2+ or lowering external Ca2+, attenuated CA1 synaptic potentials much less in challenged slices than in controls. Buffering intracellular Ca2+ by bis-( o-aminophenoxy)- N,N,N′,N′-tetraacetic acid-AM (BAPTA-AM) attenuated CA1 synaptic potentials in control but not in slices post HH. Furthermore, minimally evoked excitatory postsynaptic currents displayed a lower failure rate in post-hypoxic CA1 neurons compared with controls. Based on these convergent observations, we suggest that evoked CA1 glutamate transmission is altered in the first several hours after brief hypoxia, likely resulting from alterations in intracellular Ca2+homeostasis and/or Ca2+-dependent processes governing transmitter release.

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