Chronic Memory Deficits Research Articles

Duration of post-traumatic amnesia is uniquely associated with memory functioning in chronic moderate-to-severe traumatic brain injury

Disrupted memory circuitry may contribute to post-traumatic amnesia (PTA) after traumatic brain injury (TBI). It is unclear whether duration of PTA (doPTA) uniquely impacts memory functioning in the chronic post-injury stage. To examine the relationship between doPTA and memory functioning, independent of other cognitive abilities, in chronic moderate-to-severe TBI. Participants were 82 individuals (median chronicity = 10.5 years) with available doPTA estimates and neuropsychological data. Composite memory, processing speed (PS), and executive functioning (EF) performance scores, as well as data on subjective memory (SM) beliefs, were extracted. DoPTA-memory associations were evaluated via linear modeling of doPTA with memory performance and clinical memory status (impaired/unimpaired), controlling for PS, EF, and demographic covariates. Interrelationships between doPTA, objective memory functioning, and SM were assessed. DoPTA was significantly related to memory performance, even after covariate adjustment. Impairment in memory, but not PS or EF, was associated with a history of longer doPTA. SM was associated with memory performance, but unrelated to doPTA. Findings suggest a specific association between doPTA-an acute injury phenomenon-and chronic memory deficits after TBI. Prospective studies are needed to understand how underlying mechanisms of PTA shape distinct outcome trajectories, particularly functional abilities related to memory processing.

Exploring the potential of Desmodium gangeticum (L.) DC. extract against spatial memory deficit in rats

Background: A few published reports demonstrated the neuroprotective effect of Desmodium gangeticum (L.) DC. in an acute model of dementia. Objective: The purpose of the present study was to evaluate the preclinical efficacy of D. gangeticum against chronic dementia when administered prophylactically. Materials and Methods: Chronic spatial memory deficit was induced in rats by aluminum chloride (AlCl3, 10 mg/kg, i.p.). Treatment with hydroalcoholic whole plant extract of D. gangeticum (DG extract) was initiated 2 week before AlCl3 challenge and continued till the 51st day after the challenge, orally at the dose of 400 mg/kg/day. The spatial memory was assessed by Morris water maze test. Hippocampal and frontal cortex acetyl cholinesterase (AChE) and oxidative stress were assessed in diseased rat brains. Results: Chronic administration of AlCl3 produced spatial memory deficit in rats. Memory impairment was manifested in rats as an increase in escape latency and D-quadrant latency whereas a decrease in total time spent in D-quadrant. These behavioral alterations were reversed significantly by the treatment with DG extract. In addition, DG extract significantly increased the island time, indicating memory improvement. DG extract corrected the declined AChE in frontal cortex and altered frontal cortex/hippocampus catalase activity. Phytochemical investigation of the DG extract revealed large content of saponins among the other phytochemicals such as tannins, alkaloids, and flavonoids. Conclusion: These results indicate the possible prophylactic potential of saponin-rich DG extract against chronic memory deficit in rats.

Differential responses to increasing numbers of mild traumatic brain injury in a rodent closed-head injury model.

Following mild traumatic brain injury (mTBI), further mild impacts can exacerbate negative outcomes. To compare chronic damage and deficits following increasing numbers of repeated mTBIs, a closed-head weight-drop model of repeated mTBI was used to deliver 1, 2 or 3 mTBIs to adult female rats at 24h intervals. Outcomes were assessed at 3months following the first mTBI. No gross motor, sensory or reflex deficits were identified (p>0.05), consistent with current literature. Cognitive function assessed using a Morris water maze revealed chronic memory deficits following 1 and 2, but not 3 mTBI compared to shams (p≤0.05). Oxidative damage to DNA was assessed immunohistochemically in the dentate hilus of the hippocampus and splenium of the corpus callosum; no changes were observed. IBA1-positive microglia were increased in size in the cortex following 1 mTBI and in the corpus callosum following 2 mTBI compared to shams (p≤0.05); no changes were observed in the dentate hilus. Glial fibrillary acidic protein (GFAP)-positive astrocyte immunoreactivity was assessed in all three brain regions and no chronic changes were observed. Integrity of myelin ultrastructure in the corpus callosum was assessed using transmission electron microscopy. G ratio was decreased following 2 mTBIs compared to shams (p≤0.05) at post hoc level only. The changing patterns of damage and deficits following increasing numbers of mTBI may reflect dynamic responses to small numbers of mTBIs or a conditioning effect such that increasing numbers of mTBIs do not necessarily result in worsening pathology. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. Cover Image for this issue: doi: 10.1111/jnc.14508.

Neuromodulatory potential of phenylpropanoids; para-methoxycinnamic acid and ethyl-p-methoxycinnamate on aluminum-induced memory deficit in rats

Para-methoxycinnamic acid (PMCA) and Ethyl-p-methoxycinnamate (EPMC) are reported to possess neuroprotective effect in reversing an acute memory deficit. However, there is a dearth of evidence for their therapeutic effect in chronic memory deficit. Thus, there is a scope to study these derivatives against the chronic model of cognitive dysfunction. The present study was aimed to determine the cognitive enhancing activity of PMCA and EPMC in aluminum-induced chronic dementia. Cognitive enhancing property of PMCA and EPMC was assessed using Morris water maze by analyzing spatial memory parameters such as escape latency, D-quadrant latency, and island entries. To find a possible mechanism, the effect of test compounds on altered acetylcholinesterase (AChE) activity and oxidative stress was determined in the hippocampus and frontal cortex of rats. Docking interaction of these derivatives with acetylcholinesterase enzyme and glutamate receptors was also studied. Treatment with PMCA and EPMC showed a significant improvement in spatial memory markers and altered hippocampal AChE activity in rats with cognitive dysfunction. The implication of hippocampal and cortical oxidative stress in memory impairment was confirmed with decreased catalase/increased thiobarbituric acid reactive substances (TBARS) in rats. PMCA and EPMC reversed the oxidative stress in the brain by negatively affecting TBARS levels. Against depleted catalase levels, PMCA was more effective than EPMC in raising the depleted catalase levels. In silico analysis revealed poor affinity of EPMC and PMCA with AChE enzyme and glutamate receptor. To conclude, PMCA and EPMC exerted cognitive enhancing property independent of direct AChE and glutamate receptor inhibition.

Hippocampal Theta Dysfunction after Lateral Fluid Percussion Injury

Chronic memory deficits are a major cause of morbidity following traumatic brain injury (TBI). In the rat, the hippocampal theta rhythm is a well-studied correlate of memory function. This study sought to investigate disturbances in hippocampal theta rhythm following lateral fluid percussion injury in the rat. A total of 13 control rats and 12 TBI rats were used. Electrodes were implanted in bilateral hippocampi and an electroencephalogram (EEG) was recorded while the rats explored a new environment, and also while navigating a modified version of the Barnes maze. Theta power and peak theta frequency were significantly attenuated in the injured animals. Further, injured rats were less likely to develop a spatial strategy for Barnes maze navigation compared to control rats. In conclusion, rats sustaining lateral fluid percussion injury demonstrated deficits in hippocampal theta activity. These deficits may contribute to the underlying memory problems seen in chronic TBI.

Seizures accelerate forgetting in patients with left-sided temporal lobe epilepsy.

Ten patients with refractory temporal lobe epilepsy performed a word-position association learning task every 24 hours during video EEG monitoring. On 55 occasions recall performance was tested 30 minutes and 24 hours after the initial learning phase. Patients with left- but not right-sided temporal lobe epilepsy exhibited impaired retention of word position if a seizure had occurred during the preceding 24-hour interval. Seizures may impair the consolidation of memory in patients with left-sided temporal lobe epilepsy beyond the chronic memory deficits caused by the underlying pathology.

Chronic memory impairment after cardiac arrest outside hospital

To evaluate the nature, prevalence, and severity of chronic memory deficit in patients resuscitated after cardiac arrest outside hospital and to determine whether such deficits are related to duration of cardiac arrest. Case-control study. 35 survivors of cardiac arrest outside hospital and 35 controls matched for age and sex who had had acute myocardial infarction without cardiac arrest. Subjects assessed at least two months after index event for affective state (hospital anxiety and depression scale), premorbid intelligence (national adult reading test), short term recall (digit recall test), and episodic long term memory (Rivermead behavioural memory test). Cases and controls showed no difference in short term recall. Cases scored lower on Rivermead test than controls (mean (SD) score out of 24 points: 17.4 (5.4) v 21.8 (2.0), P < 0.001), particularly in subtests relating to verbal and spatial memory. Moderate or severe impairment was found in 37% of cases and in no controls. Severity of impairment of memory correlated significantly with measures of duration of cardiac arrest. This deficit was not significantly associated with subjects' age, interval from index event to assessment, occupation, measures of comorbidity, social deprivation, anxiety or depression scores, or estimated premorbid intelligence. Clinically important impairment of memory was common after cardiac arrest outside hospital. Improvement in response times of emergency services could reduce the severity of such deficits. With an increasing numbers of people expected to survive cardiac arrest outside hospital, rehabilitation of those with memory deficit merits specific attention.