Postischemic fish oil treatment restores long-term retrograde memory and dendritic density: An analysis of the time window of efficacy

Bacarin, Cristiano Correia; Godinho, Jaqueline; Oliveira, Rúbia Maria Weffort de; Matsushita, Makoto; Gohara, Aline Kirie; Cardozo‐Filho, Lúcio; Lima, Jéssica de Carvalho; Previdelli, Isolde Santos; Melo, Silvana Regina de; Ribeiro, Matheus Henrique Dal Molin; Milani, Humberto

doi:10.1016/j.bbr.2016.05.047

Cited by 12 publications

(6 citation statements)

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“…The effects of TGCI on spatial memory performance have been well documented [29][30][31][32]. Studies from our group showed deleterious effects of TGCI on retrograde memory in rats in the AvRM up to 39 days after the ischemic insult [33][34][35]. In the present study, memory impairments were detected up to 14 days after TGCI in rats in the AvRM and OLT.…”

Section: Discussionsupporting

confidence: 69%

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Cannabidiol Confers Neuroprotection in Rats in a Model of Transient Global Cerebral Ischemia: Impact of Hippocampal Synaptic Neuroplasticity

et al. 2021

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Evidence for the clinical use of neuroprotective drugs for the treatment of cerebral ischemia (CI) is still greatly limited. Spatial/temporal disorientation and cognitive dysfunction are among the most prominent long-term sequelae of CI. Cannabidiol (CBD) is a non-psychotomimetic constituent of Cannabis sativa that exerts neuroprotective effects against experimental CI. The present study investigated possible neuroprotective mechanisms of action of CBD on spatial memory impairments that are caused by transient global cerebral ischemia (TGCI) in rats. Hippocampal synaptic plasticity is a fundamental mechanism of learning and memory. Thus, we also evaluated the impact of CBD on neuroplastic changes in the hippocampus after TGCI. Wistar rats were trained to learn an eight-arm aversive radial maze (AvRM) task and underwent either sham or TGCI surgery. The animals received vehicle or 10 mg/kg CBD (i.p.) 30 min before surgery, 3 h after surgery, and then once daily for 14 days. On days 7 and 14, we performed a retention memory test. Another group of rats that received the same pharmacological treatment was tested in the object location test (OLT). Brains were removed and processed to assess neuronal degeneration, synaptic protein levels, and dendritic remodeling in the hippocampus. Cannabidiol treatment attenuated ischemia-induced memory de cits. In rats that were subjected to TGCI, CBD attenuated hippocampal CA1 neurodegeneration and increased brain-derived neurotrophic factor levels. Additionally, CBD protected neurons against the deleterious effects of TGCI on dendritic spine number and the length of dendritic arborization. These results suggest that the neuroprotective effects of CBD against TGCI-induced memory impairments involve changes in synaptic plasticity in the hippocampus.

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Section: Discussionsupporting

confidence: 69%

“…The extent to which the modest reduction of CA1 pyramidal loss that was elicited by CBD treatment contributes to memory preservation (or recovery) is uncertain. Fish oil treatment was reported to restore memory loss that was caused by TGCI without rescuing hippocampal CA1 pyramidal cells [24,[43][44][45].…”

Section: Discussionmentioning

confidence: 99%

Cannabidiol Confers Neuroprotection in Rats in a Model of Transient Global Cerebral Ischemia: Impact of Hippocampal Synaptic Neuroplasticity

et al. 2021

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“…Nevertheless, functional recovery has not always been linked to protection at a cellular level, including neurons. Ultrastructural changes at a subcellular level, including dendritic restructuring, reactive synaptogenesis, and growth-promoting processes, may also be involved in functional rescue after cerebral ischemia (Bacarin et al, 2016;García-Chávez et al, 2008;Godinho et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Roflumilast protects against spatial memory impairments and exerts anti‐inflammatory effects after transient global cerebral ischemia

Bonato

Meyer

Mendonça

et al. 2021

Eur J of Neuroscience

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Phosphodiesterase 4 (PDE4) inhibitors have been shown to present beneficial effects in cerebral ischemic injury because of their ability to improve cognition and target different phases and mechanisms of cerebral ischemia, including apoptosis, neurogenesis, angiogenesis, and inflammation. The present study investigated whether repeated treatment with the PDE4 inhibitor roflumilast rescued memory loss and attenuated neuroinflammation in rats following transient global cerebral ischemia (TGCI). TGCI caused memory impairments, neuronal loss (reflected by Neuronal nuclei (NeuN) immunoreactivity), and compensatory neurogenesis (reflected by doublecortin (DCX) immunoreactivity) in the hippocampus. Also, increases in the protein expression of the phosphorylated response element-binding protein (pCREB) and inflammatory markers such as the glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba-1), were detected in the hippocampus in TGCI rats. Repeated treatment with roflumilast (0.003 and 0.01 mg/kg) prevented spatial memory deficits without promoting hippocampal protection in ischemic animals. Roflumilast increased the levels of pCREB, arginase-1, interleukin (IL) 4, and IL-10 in the hippocampus 21 days after TGCI. These data suggest a protective effect of roflumilast against functional sequelae of cerebral ischemia, which might be related to its anti-inflammatory properties.

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“…Cytokine release, and altered levels of cyclooxygenase-2 (COX-2), hypoxia-inducible factor 1alpha and inducible nitric oxide synthase were indicated as mechanisms for the beneficial effects [32,46], and suggests a shift from pro-inflammatory to antiinflammatory (or pro-resolving) polarization of microglia [45,47]. Post-stroke administration of n-3 PUFAs were also shown to reduce mortality rate in mice subjected to MCAO [48], and to enhance long-term neurogenesis [49] as well as cognitive and behavioural recovery after stroke [50,51].…”

Section: Intervention In Experimental Stroke Modelsmentioning

confidence: 99%

Role of polyunsaturated fatty acids in ischemic stroke – A perspective of specialized pro-resolving mediators

Miao¹,

Schultzberg²,

Wang³

et al. 2021

Clinical Nutrition

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Polyunsaturated fatty acids (PUFAs) have been proposed as beneficial for cardiovascular health. However, results from both epidemiological studies and clinical trials have been inconsistent, whereas most of the animal studies showed promising benefits of PUFAs in the prevention and treatment of ischemic stroke. In recent years, it has become clear that PUFAs are metabolized into various types of bioactive derivatives, including the specialized pro-resolving mediators (SPMs). SPMs exert multiple biofunctions, such as to limit excessive inflammatory responses, regulate lipid metabolism and immune cell functions, decrease production of pro-inflammatory factors, increase anti-inflammatory mediators, as well as to promote tissue repair and homeostasis. Inflammation has been recognised as a key contributor to the pathophysiology of acute ischemic stroke. Owing to their potent pro-resolving actions, SPMs are potential for development of novel anti-stroke therapy. In this review, we will summarize current knowledge of epidemiological studies, basic research and clinical trials concerning PUFAs in stroke prevention and treatment, with special attention to SPMs as the unsung heroes behind PUFAs.

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Postischemic fish oil treatment restores long-term retrograde memory and dendritic density: An analysis of the time window of efficacy

Cited by 12 publications

References 53 publications

Cannabidiol Confers Neuroprotection in Rats in a Model of Transient Global Cerebral Ischemia: Impact of Hippocampal Synaptic Neuroplasticity

Cannabidiol Confers Neuroprotection in Rats in a Model of Transient Global Cerebral Ischemia: Impact of Hippocampal Synaptic Neuroplasticity

Roflumilast protects against spatial memory impairments and exerts anti‐inflammatory effects after transient global cerebral ischemia

Role of polyunsaturated fatty acids in ischemic stroke – A perspective of specialized pro-resolving mediators

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