Recent advances in the development of neuroprotective agents and therapeutic targets in the treatment of cerebral ischemia

Luo, Yin; Tang, Haishuang; He, Li; Zhao, Rui; Huang, Qinghai; Liu, Jianmin

doi:10.1016/j.ejmech.2018.11.014

Cited by 58 publications

(49 citation statements)

References 146 publications

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“…The ability of tempol to reverse the detrimental effects of T in long-term castrate rats strongly implicates an interaction between oxidative stress and T in stroke outcomes. Oxidative stress has long been recognized as an important contributor to ischemic injury [70], and antioxidants and free radical scavengers can reduce experimental stroke injury [71]. The ability of tempol to reduce the detrimental effects of T in LTTD rats supports the idea that T exacerbates oxidative stress injury.…”

Section: Discussionmentioning

confidence: 92%

Chronic Testosterone Deprivation Sensitizes the Middle-Aged Rat Brain to Damaging Effects of Testosterone Replacement

et al. 2019

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Introduction: An increasing number of middle-aged men are being screened for low testosterone levels and the number of prescriptions for various forms of testosterone replacement therapy (TRT) has increased dramatically over the last 10 years. However, the safety of TRT has come into question with some studies suggesting increased morbidity and mortality. Objective: Because the benefits of estrogen replacement in postmenopausal women and ovariectomized rodents are lost if there is an extended delay between estrogen loss and replacement, we hypothesized that TRT may also be sensitive to delayed replacement. Methods: We compared the effects of testosterone replacement after shortterm (2 weeks) and long-term testosterone deprivation (LTTD; 10 weeks) in middle-aged male rats on cerebral ischemia, oxidative stress, and cognitive function. We hypothesized that LTTD would increase oxidative stress levels and abrogate the beneficial effects of TRT. Results: Hypogonadism itself and TRT after short-term castration did not affect stroke outcome compared to intact rats. However, after long-term hypogonadism in middle-aged male Fischer 344 rats, TRT exacerbated the detrimental behavioral effects of experimental focal cerebral ischemia, whereas this detrimental effect was prevented by administration of the freeradical scavenger tempol, suggesting that TRT exacerbates oxidative stress. In contrast, TRT improved cognitive performance in non-stroked rats regardless of the length of hypogonadism. In the Morris water maze, peripheral oxidative stress was highly associated with decreased cognitive ability. Conclusions: Taken together, these data suggest that TRT after long-term hypogonadism can exacerbate functional recovery after focal cerebral ischemia, but in the absence of injury can enhance cognition. Both of these effects are modulated by oxidative stress levels.

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Section: Discussionmentioning

confidence: 92%

Chronic Testosterone Deprivation Sensitizes the Middle-Aged Rat Brain to Damaging Effects of Testosterone Replacement

et al. 2019

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“…Bull. 13 C-NMR spectra were recorded at 400 and 100 MHz on a Bruker AM-400 spectrometer in chloroform-d solutions, respectively. Chemical shifts were reported in ppm (δ) and coupling constants (J) are in hertz (Hz).…”

Section: Chemicals and Materialsmentioning

confidence: 99%

“…OFT The locomotor activity of the gerbil was studied in the OFT as described in the previous study. 13) RRT The rotarod performance of the mice was studied in the RRT. Before each experiment, the gerbil was placed on the stationary rotarod for 30 s. Then the animals were given 3 trials per day for 5 consecutive days on the rod (30 rpm over 2 min).…”

Section: Chemicals and Materialsmentioning

confidence: 99%

<i>N</i>-Linoleyltyrosine Protects against Transient Cerebral Ischemia in Gerbil <i>via</i> CB2 Receptor Involvement in PI3K/Akt Signaling Pathway

Cheng

Zhou

et al. 2019

Biological & Pharmaceutical Bulletin

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Anandamide (AEA) played potent neuroprotective activities via cannabinoid type 1 (CB1) and 2 (CB2) receptor. N-Linoleyltyrosine (NITyr), as an AEA analogue, was synthesized in our laboratory and evaluated the neuroprotective effects and mechanisms for the first time. NITyr was synthesized via substitution reaction. The neuroprotective effects of NITyr were evaluated in a gerbil model of transient cerebral ischemia. Each gerbil was subjected to open field test (OFT), Rotard rod test (RRT), Morris water maze (MWM)successively and executed after animal behaviors. Part of the brain was stained with hematoxylin and eosin (HE) and Nissl staining, and the rest for biochemical analysis. NITyr could not increase spontaneous locomotor activity and ameliorate the anxiety behavior in the OFT but could improve the motor coordination in the RRT and the spatial memory impairment in the MWM. Immunohistochemically, NITyr could attenuate the ischemia-induced neural loss in the hippocampus. The Enzyme-linked immunosorbent assay (ELISA) suggested that NITyr ameliorated the inflammation and oxidative stress. Consistently, NITyr could up-regulate the expressions of p-phosphadylinositol 3-kinase (PI3K) and p-Akt but not PI3K and Akt in the hippocampus. In addition to oxidative stress, CB2 receptor antagonist AM630 but not CB1 receptor antagonist AM251 could reverse the above phenomena. However, CB1 receptor antagonist AM251 could reverse oxidative stress. Accordingly, NITyr could up-regulate the expressions of CB2 but not CB1. NITyr could improve the motor coordination, learning and memory impairments, neural loss in the hippocampus and the inflammation of the mice via CB2 receptor involvement of PI3K/Akt signaling pathway.

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“…In this approach, we will engage in the involvement of inflammation and immunity in the medical conditions that antecede acute ischemic stroke, as well as highlight how these processes are involved in the pathophysiology of the ischemic lesion once established and in the subsequent repair mechanisms [4,20]. …”

Section: Lecture Highlightsmentioning

confidence: 99%

Neuroinflammation and Neuromodulation in Neurological Diseases

Robinson-Agramonte

Gonçalves

Almeida

et al. 2019

Behavioral Sciences

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Neuroimmunology is a relatively young science. This discipline has emerged today from the research field as a mature and fully developed innovative research area that integrates not only pure topics of neuroimmunology, but also expands on wider fields such as neuroplasticity, neuronal reserve and neuromodulation in association with clinical events, amongst which behavioral disorders stand out. The Cuban School of Neuroimmunology—a recent meeting that took place in Havana, Cuba—focused on topics based on the molecular mechanisms of neuroinflammation in neurological disorders involving behavioral manifestations, such as multiple sclerosis (MS), autism, cerebellar ataxias, Alzheimer´s disease and stroke among others, as well as on the use of new interventional technologies in neurology. Professor Luis Velazquez, from the Cuban Academy of Sciences, dictated an interesting lecture on Spinocerebellar ataxias, a genetic disorder where recent hypotheses related to the influence of neuroinflammation as a neurobiological factor influencing the progression of this disease have emerged. At the same time, the use of new interventional technologies in neurology was discussed, including those referring to novel disease modifying therapies in the course of MS and the use of transcranial magnetic stimulation in several neurological diseases, the latter reinforcing how interventional strategies in the form of non-invasive bran stimulation can contribute to physical rehabilitation in neurology. This paper summarizes the highlights of the most relevant topics presented during the First Cuban School of Neuroimmunology, organized by the Cuban Network of Neuroimmunology, held in June 2019.

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Recent advances in the development of neuroprotective agents and therapeutic targets in the treatment of cerebral ischemia

Cited by 58 publications

References 146 publications

Chronic Testosterone Deprivation Sensitizes the Middle-Aged Rat Brain to Damaging Effects of Testosterone Replacement

Chronic Testosterone Deprivation Sensitizes the Middle-Aged Rat Brain to Damaging Effects of Testosterone Replacement

<i>N</i>-Linoleyltyrosine Protects against Transient Cerebral Ischemia in Gerbil <i>via</i> CB2 Receptor Involvement in PI3K/Akt Signaling Pathway

Neuroinflammation and Neuromodulation in Neurological Diseases

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