Motor and memory function in rat models of cyanide toxicity and vascular occlusion induced ischemic injury

Cerebral ischemic injury is a significant portion of the burden of disease in developed countries; rates of mortality are high and the costs associated with morbidity are enormous. Recent therapeutic approaches have aimed at mitigating the extent of damage and/or promoting repair once injury has occurred. Often, patients at high risk of ischemic injury can be identified in advance and targeted for antecedent neuroprotective therapy. Agents that stimulate the innate pattern recognition receptor, Toll-like receptor 9, have been shown to induce tolerance (precondition) to ischemic brain injury in a mouse model of stroke. Here, we demonstrate for the first time that pharmacological preconditioning against cerebrovascular ischemic injury is also possible in a nonhuman primate model of stroke in the rhesus macaque. The model of stroke used is a minimally invasive transient vascular occlusion, resulting in brain damage that is primarily localized to the cortex and as such, represents a model with substantial clinical relevance. Finally, K-type (also referred to as B-type) cytosine-guanine-rich DNA oligonucleotides, the class of agents employed in this study, are currently in use in human clinical trials, underscoring the feasibility of this treatment in patients at risk of cerebral ischemia.

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Anti-inflammatory therapy in acute periods of chronic ischemic retinal injury in rats

Nauchno-prakticheskii zhurnal «Patogenez» ◽

10.25557/gm.2017.3.8497 ◽

2017 ◽

pp. 51-57

Author(s):

Е.М. Клочихина ◽

С.А. Гаврилова

Keyword(s):

Arachidonic Acid ◽

Vascular Occlusion ◽

Ischemic Injury ◽

Retinal Ischemia ◽

Male Rats ◽

Arachidonic Acid Cascade ◽

Ischemic Disease ◽

Early Stages ◽

Retinal Injury ◽

Retinal Vascular Occlusion

Ишемия сетчатки возникает вследствие окклюзии сосудов сетчатки или как осложнение при таких заболеваниях, как диабет, глаукома, и при других патологиях. Ишемическое повреждение связано с развитием воспалительного ответа и активацией каскада арахидоновой кислоты. Цель настоящей работы состояла в изучении влияния блокады каскада арахидоновой кислоты на развитие ишемического повреждения сетчатки глаза крысы. Методы. Ишемию сетчатки моделировали путем двусторонней окклюзии внутренних сонных артерий (ВСА) у крыс-самцов линии Вистар. Через 15 минут после окклюзии ВСА вводили интравитреально (по 2 мкл) лорноксикам (неселективный блокатор циклооксигеназ), триамцинолон (блокатор фосфолипазы А2) и физиологический раствор. Кроме того, через 24 и 48 ч после окклюзии ВСА лорноксикам вводили внутрибрюшинно (230 мкг/кг) и внутримышечно триамцинолон (571 мкг/кг). Офтальмоскопию для оценки состояния глазного дна проводили до операции, через 7, 14, 28, 56 и 180 суток после окклюзии артерий. В аналогичные сроки осуществляли энуклеацию глаз для гистологического исследования. Результаты исследования показали, что лорноксикам обладает пролонгированным протекторным эффектом на ишемизированную сетчатку, в частности, замедляет истончение сетчатки и ограничивает увеличение площади неперфузируемых капиллярных зон. В то же время эффекты триамцинолона были неоднозначными, кратковременными и развивались на фоне ухудшения общего самочувствия животных. Заключение. Полученные данные свидетельствуют о возможности применения блокаторов синтеза простагландинов для терапии ишемических заболеваний сетчатки глаза. Background. Retinal ischemia results from retinal vascular occlusion or develops as a complication of diabetes mellitus, glaucoma, and various neovascular diseases. Ischemic injury is definitely related with an inflammatory response and activation of the arachidonic acid cascade. For this reason, the aim of this study was to examine the course of changes in ischemic injury of rat retina and the effect of blocking the arachidonic acid cascade at early stages. Methods. Retinal ischemia was simulated by bilateral occlusion of internal carotid arteries (ICA) in Wistar male rats. Lornoxicam (non-selective cyclooxygenase inhibitor), triamcinolone (phospholipase A2 inhibitor), and saline were injected intravitreally at 15 min following ICA bilateral occlusion and intraperitoneally at 24 h and 48 h. The fundus was examined using ophthalmoscopy before the operation and at 7, 14, 28, 56, and 180 days following the occlusion. Enucleation was conducted for histological analysis on the same days. Results. Lornoxicam administered at early stages exerted a long-term protective effect on the ischemic retina. Effects of triamcinolone were controversial, brief, and associated with impaired general state of animals. Therefore, prostaglandin synthesis inhibitors might be used as a therapy for retinal ischemic disease.

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Continuous VA deficiency during postnatal development decreases rat learning and memory function via excitatory Ca2+neuron

Cell Biology International ◽

10.1042/cbi034s018a ◽

2010 ◽

Vol 34 (8) ◽

pp. S18-S18

Author(s):

Wei Jiang ◽

Enyi Wen ◽

Min Gong ◽

Yang Bi ◽

Xiaojuan Zhang ◽

...

Keyword(s):

Postnatal Development ◽

Learning And Memory ◽

Memory Function

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Folate and vitamin B-12 deficiencies additively impaired memory function and disturbed the gut microbiota in amyloid-β infused rats

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000624 ◽

2019 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Sunmin Park ◽

Sunna Kang ◽

Da Sol Kim

Keyword(s):

Insulin Resistance ◽

Gut Microbiota ◽

Insulin Signaling ◽

Gut Microbiome ◽

Metabolic Diseases ◽

Memory Function ◽

Amyloid Β ◽

Impaired Memory ◽

Ca1 Region ◽

Folate And Vitamin B12

Abstract. Folate and vitamin B12(V-B12) deficiencies are associated with metabolic diseases that may impair memory function. We hypothesized that folate and V-B12 may differently alter mild cognitive impairment, glucose metabolism, and inflammation by modulating the gut microbiome in rats with Alzheimer’s disease (AD)-like dementia. The hypothesis was examined in hippocampal amyloid-β infused rats, and its mechanism was explored. Rats that received an amyloid-β(25–35) infusion into the CA1 region of the hippocampus were fed either control(2.5 mg folate plus 25 μg V-B12/kg diet; AD-CON, n = 10), no folate(0 folate plus 25 μg V-B12/kg diet; AD-FA, n = 10), no V-B12(2.5 mg folate plus 0 μg V-B12/kg diet; AD-V-B12, n = 10), or no folate plus no V-B12(0 mg folate plus 0 μg V-B12/kg diet; AD-FAB12, n = 10) in high-fat diets for 8 weeks. AD-FA and AD-VB12 exacerbated bone mineral loss in the lumbar spine and femur whereas AD-FA lowered lean body mass in the hip compared to AD-CON(P < 0.05). Only AD-FAB12 exacerbated memory impairment by 1.3 and 1.4 folds, respectively, as measured by passive avoidance and water maze tests, compared to AD-CON(P < 0.01). Hippocampal insulin signaling and neuroinflammation were attenuated in AD-CON compared to Non-AD-CON. AD-FAB12 impaired the signaling (pAkt→pGSK-3β) and serum TNF-α and IL-1β levels the most among all groups. AD-CON decreased glucose tolerance by increasing insulin resistance compared to Non-AD-CON. AD-VB12 and AD-FAB12 increased insulin resistance by 1.2 and 1.3 folds, respectively, compared to the AD-CON. AD-CON and Non-AD-CON had a separate communities of gut microbiota. The relative counts of Bacteroidia were lower and those of Clostridia were higher in AD-CON than Non-AD-CON. AD-FA, but not V-B12, separated the gut microbiome community compared to AD-CON and AD-VB12(P = 0.009). In conclusion, folate and B-12 deficiencies impaired memory function by impairing hippocampal insulin signaling and gut microbiota in AD rats.

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Impact of Comorbid Depression on Serial Position Effects in Alzheimer’s Disease

GeroPsych ◽

10.1024/1662-9647/a000115 ◽

2014 ◽

Vol 27 (4) ◽

pp. 161-169 ◽

Cited By ~ 1

Author(s):

Nienke A. Hofrichter ◽

Sandra Dick ◽

Thomas G. Riemer ◽

Carsten Schleussner ◽

Monique Goerke ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Serial Position ◽

Episodic Memory ◽

Memory Performance ◽

Memory Function ◽

Word List ◽

Position Effects ◽

Serial Position Effects ◽

List Memory

Hippocampal dysfunction and deficits in episodic memory have been reported for both Alzheimer’s disease (AD) and major depressive disorder (MDD). Primacy performance has been associated with hippocampus-dependent episodic memory, while recency may reflect working memory performance. In this study, serial position profiles were examined in a total of 73 patients with MDD, AD, both AD and MDD, and healthy controls (HC) by means of CERAD-NP word list memory. Primacy performance was most impaired in AD with comorbid MDD, followed by AD, MDD, and HC. Recency performance, on the other hand, was comparable across groups. These findings indicate that primacy in AD is impaired in the presence of comorbid MDD, suggesting additive performance decrements in this specific episodic memory function.

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