Alkaline brain pH shift in rodent lithium-pilocarpine model of epilepsy with chronic seizures

2021 ◽  
Vol 1758 ◽  
pp. 147345
Author(s):  
Dongshuang Lu ◽  
Yang Ji ◽  
Padmavathi Sundaram ◽  
Roger D. Traub ◽  
Yuguang Guan ◽  
...  
Keyword(s):  
Ph Shift ◽  
2019 ◽  
Vol 16 (7) ◽  
pp. 637-644 ◽  
Author(s):  
Hadas Han ◽  
Sara Eyal ◽  
Emma Portnoy ◽  
Aniv Mann ◽  
Miriam Shmuel ◽  
...  

Background: Inflammation is a hallmark of epileptogenic brain tissue. Previously, we have shown that inflammation in epilepsy can be delineated using systemically-injected fluorescent and magnetite- laden nanoparticles. Suggested mechanisms included distribution of free nanoparticles across a compromised blood-brain barrier or their transfer by monocytes that infiltrate the epileptic brain. Objective: In the current study, we evaluated monocytes as vehicles that deliver nanoparticles into the epileptic brain. We also assessed the effect of epilepsy on the systemic distribution of nanoparticleloaded monocytes. Methods: The in vitro uptake of 300-nm nanoparticles labeled with magnetite and BODIPY (for optical imaging) was evaluated using rat monocytes and fluorescence detection. For in vivo studies we used the rat lithium-pilocarpine model of temporal lobe epilepsy. In vivo nanoparticle distribution was evaluated using immunohistochemistry. Results: 89% of nanoparticle loading into rat monocytes was accomplished within 8 hours, enabling overnight nanoparticle loading ex vivo. The dose-normalized distribution of nanoparticle-loaded monocytes into the hippocampal CA1 and dentate gyrus of rats with spontaneous seizures was 176-fold and 380-fold higher compared to the free nanoparticles (p<0.05). Seizures were associated with greater nanoparticle accumulation within the liver and the spleen (p<0.05). Conclusion: Nanoparticle-loaded monocytes are attracted to epileptogenic brain tissue and may be used for labeling or targeting it, while significantly reducing the systemic dose of potentially toxic compounds. The effect of seizures on monocyte biodistribution should be further explored to better understand the systemic effects of epilepsy.


2013 ◽  
Vol 129 (1) ◽  
pp. 107-119 ◽  
Author(s):  
Mussie G. Hadera ◽  
Olav B. Smeland ◽  
Tanya S. McDonald ◽  
Kah Ni Tan ◽  
Ursula Sonnewald ◽  
...  

2014 ◽  
Vol 61 ◽  
pp. 32-39 ◽  
Author(s):  
Kerstin J. Frank ◽  
Kathrin Locher ◽  
Damir E. Zecevic ◽  
Jeannine Fleth ◽  
Karl G. Wagner
Keyword(s):  
Ph Shift ◽  

2007 ◽  
Vol 25 (1) ◽  
pp. 80-91 ◽  
Author(s):  
Boyoung Lee ◽  
Heather Dziema ◽  
Kyu Hyun Lee ◽  
Yun-Sik Choi ◽  
Karl Obrietan

2015 ◽  
Vol 113 (7) ◽  
pp. 2840-2844 ◽  
Author(s):  
Pariya Salami ◽  
Maxime Lévesque ◽  
Jean Gotman ◽  
Massimo Avoli

Low-voltage fast (LVF)- and hypersynchronous (HYP)-seizure onset patterns can be recognized in the EEG of epileptic animals and patients with temporal lobe epilepsy. Ripples (80–200 Hz) and fast ripples (250–500 Hz) have been linked to each pattern, with ripples predominating during LVF seizures and fast ripples predominating during HYP seizures in the rat pilocarpine model. This evidence led us to hypothesize that these two seizure-onset patterns reflect the contribution of neural networks with distinct transmitter signaling characteristics. Here, we tested this hypothesis by analyzing the seizure activity induced with the K+ channel blocker 4-aminopyridine (4AP, 4–5 mg/kg ip), which enhances both glutamatergic and GABAergic transmission, or the GABAA receptor antagonist picrotoxin (3–5 mg/kg ip); rats were implanted with electrodes in the hippocampus, the entorhinal cortex, and the subiculum. We found that LVF onset occurred in 82% of 4AP-induced seizures whereas seizures after picrotoxin were always HYP. In addition, high-frequency oscillation analysis revealed that 4AP-induced LVF seizures were associated with higher ripple rates compared with fast ripples ( P < 0.05), whereas picrotoxin-induced seizures contained higher rates of fast ripples compared with ripples ( P < 0.05). These results support the hypothesis that two distinct patterns of seizure onset result from different pathophysiological mechanisms.


1986 ◽  
Vol 65 (5) ◽  
pp. 693-696 ◽  
Author(s):  
W. Richard Marsh ◽  
Robert E. Anderson ◽  
Thoralf M. Sundt

✓ The adverse effect of a minimal cerebral blood flow (CBF) in models of global ischemia has been noted by many investigators. One factor believed important in this situation is the level of blood glucose, since a continued supply of this metabolite results in increased tissue lactate, decreased brain pH, and increased cell damage. The authors have extended these observations to a model of focal incomplete ischemia. Brain pH was measured in fasted squirrel monkeys in regions of focal incomplete ischemia after transorbital occlusion of the middle cerebral artery (MCA). In both control and hyperglycemic animals, CBF was reduced to less than 30% of baseline. At 3 hours after MCA occlusion, brain pH in the control group was 6.66 ± 0.68 as compared to 6.27 ± 0.26 in the glucose-treated group. This difference was statistically significant by Student's unpaired t-test (p < 0.05). Thus, hyperglycemia results in decreased tissue pH in regions of focal incomplete cerebral ischemia in monkeys.


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