Author response for "Progressive Long‐term Spatial Memory Loss following Repeat Concussive and Subconcussive Brain Injury in Mice, Associated with Dorsal Hippocampal Neuron Loss, Microglial Phenotype Shift, and Vascular Abnormalities"

Hypoxic–ischemic brain damage (HIBD) is one of the leading causes of brain injury in infant with high risk of mortality and disability; therefore, it is important to explore more feasible and effective treatment strategies. Here, we assessed the neuroprotective effects of different hydrogen inhalation times for the treatment of HIBD. We induced hypoxia–ischemia in Sprague–Dawley rats (postnatal day 7, both sexes), followed by treatment with hydrogen inhalation for 30, 60, or 90 min. Morphological brain injury was assessed by Nissl and TUNEL staining. Acute inflammation was evaluated by examining the expression of interleukin-1β (IL-1β) and NF-κB p65, as well as Iba-1 immunofluorescence in the brain. Neural apoptosis was evaluated by examining the expression of P-JNK and p53 as well as NeuN immunofluorescence. Neurobehavioral function of rats was evaluated by Morris water maze test at 36 days after surgery. The results showed that hypoxia–ischemia injury induced the inflammatory response of microglia; however, these changes were inhibited by hydrogen inhalation. The inhibitory effects became more apparent as the treatment duration increased ( P < 0.05). Furthermore, hypoxia–ischemia induced neuronal damage and increased the expression of the apoptotic factors, P-JNK, and p53, which were attenuated by hydrogen inhalation ( P < 0.05). Hypoxia–ischemia caused long-term spatial memory deficits during brain maturation, which were ameliorated by hydrogen inhalation ( P < 0.01). In conclusion, hypoxia–ischemia induced severe long-term damage to the brain, which could be alleviated by hydrogen inhalation in a time-dependent manner. Impact statement Oxidative stress is known to be involved in the main pathological progression of neonatal hypoxic–ischemic brain damage (HIBD). Hydrogen (H2) is an antioxidant that can be used to treat HIBD; however, the mechanism by which hydrogen may be used as a promising treatment for neonates with HIBD is not very clear. This study demonstrated that inhaled H2 is neuroprotective against HIBD in SpragueDawley rats by inhibiting the brain’s inflammatory response and neuronal apoptosis or damage and protecting against spatial memory decline. Further, this study showed that inhaled H2 has potential as a therapeutic approach for HIBD. This is relevant to clinical treatment protocols when hypoxia–ischemia is suspected in neonates.

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Sustained dorsal hippocampal activity is not obligatory for either the maintenance or retrieval of long-term spatial memory

Hippocampus ◽

10.1002/hipo.20722 ◽

2010 ◽

Vol 20 (12) ◽

pp. 1366-1375 ◽

Cited By ~ 9

Author(s):

Nicola J. Broadbent ◽

Larry R. Squire ◽

Robert E. Clark

Keyword(s):

Spatial Memory ◽

Dorsal Hippocampal ◽

Hippocampal Activity

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Long-term caffeine treatment of Alzheimer mouse models ameliorates behavioural deficits and neuron loss and promotes cellular and molecular markers of neurogenesis

Cellular and Molecular Life Sciences ◽

10.1007/s00018-021-04062-8 ◽

2021 ◽

Author(s):

Martina Stazi ◽

Sandra Lehmann ◽

M. Sadman Sakib ◽

Tonatiuh Pena-Centeno ◽

Luca Büschgens ◽

...

Keyword(s):

Mouse Models ◽

Hippocampal Neuron ◽

Amyloid Β ◽

Synaptic Function ◽

Sequencing Analysis ◽

Behavioral Deficits ◽

Altered Expression ◽

Neuron Loss ◽

App Processing

AbstractEpidemiological studies indicate that the consumption of caffeine, the most commonly ingested psychoactive substance found in coffee, tea or soft drinks, reduces the risk of developing Alzheimer’s disease (AD). Previous treatment studies with transgenic AD mouse models reported a reduced amyloid plaque load and an amelioration of behavioral deficits. It has been further shown that moderate doses of caffeine have the potential to attenuate the health burden in preclinical mouse models of a variety of brain disorders (reviewed in Cunha in J Neurochem 139:1019–1055, 2016). In the current study, we assessed whether long-term caffeine consumption affected hippocampal neuron loss and associated behavioral deficits in the Tg4-42 mouse model of AD. Treatment over a 4-month period reduced hippocampal neuron loss, rescued learning and memory deficits, and ameliorated impaired neurogenesis. Neuron-specific RNA sequencing analysis in the hippocampus revealed an altered expression profile distinguished by the up-regulation of genes linked to synaptic function and processes, and to neural progenitor proliferation. Treatment of 5xFAD mice, which develop prominent amyloid pathology, with the same paradigm also rescued behavioral deficits but did not affect extracellular amyloid-β (Aβ) levels or amyloid precursor protein (APP) processing. These findings challenge previous assumptions that caffeine is anti-amyloidogenic and indicate that the promotion of neurogenesis might play a role in its beneficial effects.

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Erythropoietin improves long-term spatial memory deficits and brain injury following neonatal hypoxia–ischemia in rats

Behavioural Brain Research ◽

10.1016/j.bbr.2003.11.002 ◽

2004 ◽

Vol 153 (1) ◽

pp. 77-86 ◽

Cited By ~ 140

Author(s):

Abdullah Kumral ◽

Nazan Uysal ◽

Kazim Tugyan ◽

Atac Sonmez ◽

Osman Yilmaz ◽

...

Keyword(s):

Brain Injury ◽

Spatial Memory ◽

Memory Deficits ◽

Neonatal Hypoxia ◽

Hypoxia Ischemia

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