Postischemic fish oil treatment confers task-dependent memory recovery

Abstract

A series of our previous studies demonstrated that fish oil (FO), equivalent to 300mg/kg docosahexahenoic acid (DHA), facilitates memory recovery after transient, global cerebral ischemia (TGCI) in the aversive radial maze (AvRM). The present study sought to address two main issues: (i) whether the memory-protective effect of FO that has been observed in the AvRM can be replicated in the passive avoidance test (PAT) and object location test (OLT) and (ii) whether FO at doses that are lower than those used previously can also prevent TGCI-induced memory loss. In Experiment 1, naive rats were trained in the PAT, subjected to TGCI (4-vessel occlusion model), and tested for retrograde memory performance 8 and 15days after ischemia. Fish oil (300mg/kg/day DHA) was given orally for 8days. The first dose was delivered 4h postischemia. In Experiment 2, the rats were subjected to TGCI, treated with the same FO regimen, and then trained and tested in the OLT. In Experiment 3, the rats were trained in the AvRM, subjected to TGCI, administered FO (100, 200, and 300mg/kg DHA), and tested for memory performance up to 3weeks after TGCI. At the end of the behavioral tests, the brains were examined for neurodegeneration and neuroblast proliferation. All of the behavioral tests (PAT, OLT, and AvRM) were sensitive to ischemia, but only the AvRM was able to detect the memory-protective effect of FO. Ischemia-induced neurodegeneration and neuroblast proliferation were unaffected by FO treatment. These results suggest that (i) the beneficial effect of FO on memory recovery after TGCI is task-dependent, (ii) doses of FO<300mg/kg DHA can protect memory function in the radial maze, and (iii) cognitive recovery occurs in the absence of neuronal rescue and/or hippocampal neurogenesis.

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

“…Spatial memory deficits have been associated with TGCI in several animal models with primarily damage to CA1 of the hippocampus. T-maze (Babcock & Graham-Goodwin, 1997), Morris water mazer (Block et al, 1999), and aversive radial maze (De Oliveira et al, 2017;Langdon et al, 2008;Paganelli et al, 2004) have been used in assessing TGCIassociated spatial memory deficits. In studies using these models, the CA1 hippocampal cell loss range from 30% to 80%.…”

“…As a compensatory response, adult hippocampal neurogenesis contributes to the cerebral repair and functional recovery following experimental cerebral ischemia (de Oliveira et al, 2017;Lei et al, 2014;Mori et al, 2017;Schiavon et al, 2010). In most situations, however, neurogenesis that is induced by cerebral ischemia is limited and insufficient to promote functional recovery (Wang et al, 2018;Zhang et al, 2004).…”

WITHDRAWN: Angelica Sinensis Extract Protects Against Memory Deficits by Promoting P38 MAPK–mediated Hippocampal Neurogenesis and Neuronal Survival in the Chronic Phase of Transient Global Cerebral Ischemia in Rats

“…Various clinical conditions, including reversible cardiac arrest and diseases related to reduced blood ow to the brain, induce transient global cerebral ischemia (GCI). Transient GCI frequently causes long-lasting cognitive impairments, principally memory and learning dysfunction, and contributes to the development of neurological disorders, such as vascular dementia [1,2]. Hippocampal cornu ammonis 1 (CA1) neurons are selectively vulnerable and undergo delayed degeneration in response to ischemic injury.…”

“…The newborn neurons subsequently provide cell replacement, thereby exerting a compensatory effect after ischemic stroke [10,17]. Thus, neurogenesis from progenitor cells occurs in the hippocampal DG as a compensatory action to brain insults, such as GCI [1,18]. Bromodeoxyuridine (BrdU) is a synthetic analog of thymidine that can be incorporated into DNA in the synthesis phase of the cell cycle, and it is widely used as an indicator of cell proliferation in living tissues and as a marker of neurogenesis [18].…”

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

“…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].…”