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.

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.

Reduced Voltage-Dependent Ca2+ Signaling in CA1 Neurons After Brief Ischemia in Gerbils

1999 ◽  
Vol 81 (1) ◽  
pp. 299-306 ◽  
Author(s):  
John A. Connor ◽  
Seddigheh Razani-Boroujerdi ◽  
Anders C. Greenwood ◽  
Robert J. Cormier ◽  
Jeffrey J. Petrozzino ◽  
...  
Keyword(s):  
Direct Evidence ◽  
Large Fraction ◽  
Critical Role ◽  
Brain Slices ◽  
Ischemic Insult ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
New Perspective

Connor, J. A., S. Razani-Boroujerdi, A. C. Greenwood, R. J. Cormier, J. J. Petrozzino, and R.C.S. Lin. Reduced voltage-dependent Ca2+ signaling in CA1 neurons after brief ischemia in gerbils. J. Neurophysiol. 81: 299–306, 1999. An initial overload of intracellular Ca2+ plays a critical role in the delayed death of hippocampal CA1 neurons that die a few days after transient ischemia. Without direct evidence, the prevailing hypothesis has been that Ca2+ overload may recur until cell death. Here, we report the first measurements of intracellular Ca2+ in living CA1 neurons within brain slices prepared 1, 2, and 3 days after transient (5 min) ischemia. With no sign of ongoing Ca2+ overload, voltage-dependent Ca2+ transients were actually reduced after 2–3 days of reperfusion. Resting Ca2+ levels and recovery rate after loading were similar to neurons receiving no ischemic insult. The tetrodotoxin-insensitive Ca spike, normally generated by these neurons, was absent at 2 days postischemia, as was a large fraction of Ca2+-dependent spike train adaptation. These surprising findings may lead to a new perspective on delayed neuronal death and intervention.

Hyperexcitability of hippocampal CA1 region in brain slices after GABA withdrawal

1992 ◽  
Vol 147 (2) ◽  
pp. 229-232 ◽  
Author(s):  
G. García-Ugalde ◽  
E. Galarraga ◽  
J. Bargas ◽  
S. Brailowsky
Keyword(s):  
Brain Slices ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1

scholarly journals Calretinin expression in hippocampus of mouse offspring from dams treated with β-hydroxy-β-methylbutyrate

2016 ◽  
Vol 72 (7) ◽  
pp. 423-429 ◽  
Author(s):  
Aleksandra Krawczyk ◽  
Karol Rycerz ◽  
Jadwiga Jaworska-Adamu ◽  
Ewa Tomaszewska ◽  
Piotr Dobrowolski
Keyword(s):  
Dentate Gyrus ◽  
Cognitive Processes ◽  
Specific Antibody ◽  
Light Microscope ◽  
Brain Slices ◽  
Male Mice ◽  
Expression Intensity ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1

The aim of the study was the immunohistochemical evaluation of calretinin (CR) expression in the hippocam-pus of neonatal (P0) and 21-day-old (P21) male mice from dams that received 0.2 g/kg b.w./day of β-hydroxy-β-methylbutyrate between the 26th and 39th day of pregnancy. The immunohistochemical peroxidase-antiperoxidase reaction was conducted on brain slices of offspring from control (C) and experimental (HMB) groups, using the specific antibody against CR. CR-immunopositive neurons of the hippocampal CA1 region and the dentate gyrus with the hilus were qualitatively and quantitatively assessed by means of an Olympus BX51 light microscope and the ImageJ 1.48v program. To demonstrate statistically significant differences, the Kruskal-Wallis test was used. The results of our studies revealed a decrease in CR expression intensity and the number of neurons only in the hilus of the dentate gyrus in both groups of mice (P0 and P21). The results indi-cate that HMB administration to pregnant dams may lead to damage or even loss of CR-immunopositive neu-rons in their offspring. This phenomenon may be related to calcium excess. Cells with CR expression inhibit the activity of other interneurons, causing a reverse of inhibition in principal neurons. The loss of cells with CR ex-pression may interfere with the control and synchronisation of neuron excitability. In consequence, this may affect cognitive processes, memory and animal behaviour.

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.

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