Ethyl-acetate fraction of Trichilia catigua restores long-term retrograde memory and reduces oxidative stress and inflammation after global cerebral ischemia in rats.

We originally reported that an ethyl-acetate fraction (EAF) of Trichilia catigua prevented the impairment of water maze learning and hippocampal neurodegeneration after transient global cerebral (TGCI) in mice. We extended that previous study by evaluating whether T. catigua (i) prevents the loss of long-term retrograde memory assessed in the aversive radial maze (AvRM), (ii) confers hippocampal and cortical neuroprotection, and (iii) mitigates oxidative stress and neuroinflammation in rats that are subjected to the four vessel occlusion (4-VO) model of TGCI. In the first experiment, naive rats were trained in the AvRM and then subjected to TGCI. The EAF was administered orally 30min before and 1h after TGCI, and administration continued once per day for 7days post-ischemia. In the second experiment, the EAF was administered 30min before and 1h after TGCI, and protein carbonylation and myeloperoxidase (MPO) activity were assayed 24h and 5days later, respectively. Retrograde memory performance was assessed 8, 15, and 21days post-ischemia. Ischemia caused persistent retrograde amnesia, and this effect was prevented by T. catigua. This memory protection (or preservation) persisted even after the treatment was discontinued, despite the absence of histological neuroprotection. Protein carbonyl group content and MPO activity increased around 43% and 100%, respectively, after TGCI, which were abolished by the EAF of T. catigua. The administration of EAF did not coincide with the days of memory testing. The data indicate that antioxidant and/or antiinflammatory actions in the early phase of ischemia/reperfusion contribute to the long-term antiamnesic effect of T. catigua.

Acute Onset Vascular Dementia with Bi-Thalamic Infarct in an HIV-Positive Subject.

BACKGROUND Bi-thalamic infarctions are rare and marked by clinical polymorphism. Their association with HIV has never been reported. CASE REPORT We report a 51-year-old right-handed man with no medical history, who presented an acute onset vascular dementia associated with an antero-retrograde amnesia, a word-finding difficulty, and a dysexecutive syndrome. The CT scan was normal. Brain MRI revealed a paramedian and bi-thalamic infarction, evoking an occlusion of the Percheron artery. The electrocardiogram, transthoracic and transesophageal cardiac ultrasound, and Doppler echo of cervical arteries gave normal results. The biological work-up revealed a positive serology to HIV1. The patient was lost to follow-up and was reported dead 2 months later from an unknown cause. CONCLUSIONS This case illustrates the need to perform an HIV serology in the presence of a bi-thalamic infarction with no obvious cause, particularly in a young subject.

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

We reported that fish oil (FO) prevented the loss of spatial memory caused by transient, global cerebral ischemia (TGCI), provided the treatment covered the first days prior to and after ischemia. Continuing these studies, trained rats were subjected to TGCI, and FO was administered for 10days, with a time window of efficacy (TWE) of 4, 8 or 12h post-ischemia. Retrograde memory was assessed up to 43days after TGCI. In another experiment, ischemic rats received FO with a 4- or 12-h TWE, and dendritic density was assessed in the hippocampus and cerebral cortex. The brain lipid profile was evaluated in sham-operated and ischemic rats that were treated with FO or vehicle with a 4-h TWE. Ischemia-induced retrograde amnesia was prevented by FO administration that was initiated with either a 4- or 8-h TWE. Fish oil was ineffective after a 12-h TWE. Independent of the TWE, FO did not prevent ischemic neuronal death. In the hippocampus, but not cerebral cortex, TGCI-induced dendritic loss was prevented by FO with a 4-h TWE but not 12-h TWE. The level of docosahexaenoic acid almost doubled in the hippocampus in ischemic, FO-treated rats (4-h TWE). The data indicate that (i) the anti-amnesic effect of FO can be observed with a TWE of up to 8h, (ii) the stimulation of dendritic neuroplasticity may have contributed to this effect, and (iii) DHA in FO may be the main active constituent in FO that mediates the cognitive and neuroplasticity effects on TGCI.

Robust and enduring atorvastatin-mediated memory recovery following the 4-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion in middle-aged rats.

Chronic cerebral hypoperfusion (CCH) is a common condition associated with the development and/or worsening of age-related dementia.We previously reported persistent memory loss and neurodegeneration after CCH in middle-aged rats. Statin-mediated neuroprotection has been reported after acute cerebral ischemia. Unknown, however, is whether statins can alleviate the outcome of CCH. The present study investigated whether atorvastatin attenuates the cognitive and neurohistological outcome of CCH. Rats (12­15 months old) were trained in a non-food-rewarded radial maze, and then subjected to CCH. Atorvastatin (10 mg/kg, p.o.) was administered for 42 days or 15 days, beginning 5 h after the first occlusion stage. Retrograde memory performance was assessed at 7, 14, 21, 28, and 35 days of CCH, and expressed by "latency," "number of reference memory errors" and "number of working memory errors." Neurodegeneration was then examined at the hippocampus and cerebral cortex. Compared to sham, CCH caused profound and persistent memory loss in the vehicle-treated groups, as indicated by increased latency (91.2% to 107.3%) and number of errors (123.5% to 2508.2%), effects from which the animals did not spontaneously recover across time. This CCH-induced retrograde amnesia was completely prevented by atorvastatin (latency: −4.3% to 3.3%; reference/working errors: −2.5% to 45.7%), regardless of the treatment duration. This effect was sustained during the entire behavioral testing period (5 weeks), even after discontinuing treatment. This robust and sustained memory-protective effect of atorvastatin occurred in the absence of neuronal rescue (39.58% to 56.45% cell loss). We suggest that atorvastatin may be promising for the treatment of cognitive sequelae associated with CCH.

What does a comparison of the alcoholic Korsakoff syndrome and thalamic infarction tell us about thalamic amnesia?

In this review, the clinical, neuropsychological, and neuroimaging findings in the alcoholic Korsakoff syndrome and in thalamic amnesia, resulting from focal infarction, are compared. In both disorders, there is controversy over what is the critical site for anterograde amnesia to occur-damage to the anterior thalamus/mammillo-thalamic tract has most commonly been cited, but damage to the medio-dorsal nuclei has also been advocated. Both syndromes show 'core' features of an anterograde amnesic syndrome; but retrograde amnesia is generally much more extensive (going back many years or decades) in the Korsakoff syndrome. Likewise, spontaneous confabulation occurs more commonly in the Korsakoff syndrome, although seen in only a minority of chronic cases. These differences are attributed to the greater prevalence of frontal atrophy and frontal damage in Korsakoff cases.

Fish oil provides a sustained antiamnesic effect after acute, transient forebrain ischemia but not after chronic cerebral hypoperfusion in middle-aged rats.

We reported that fish oil (FO) abolishes retrograde amnesia consistently following transient global cerebral ischemia (TGCI) in young rats, provided it covered the first days prior to and after ischemia. Here, we further evaluated whether FO given post-ischemia in older rats (15-18 months old) is equally effective in facilitating memory recovery. We also tested whether the antiamnesic effect of FO observed after TGCI can be reproduced after chronic cerebral hypoperfusion (CCH). FO (300 mg/kg docosahexaenoic acid [DHA]) was delivered orally 4h after TGCI and continued once per day for 9 days. In the CCH group, FO treatment began soon after the first stage of 4-VO/ICA and continued daily for 43 days. Two weeks after surgery, the animals were tested for retrograde memory performance across 5 weeks. Both TGCI and CCH caused persistent memory impairment and hippocampal and cortical neurodegeneration. TGCI-induced retrograde amnesia was reversed by FO, an effect that was sustained for at least 5 weeks after discontinuing treatment. In contrast, the memory deficit caused by CCH remained unchanged after FO treatment. Both hippocampal and cortical damage was not alleviated by FO. We conclude that the FO-mediated antiamnesic effect following TGCI can be extended to older rats, even when the treatment begins 4h postischemia. Such efficacy was not reproduced after CCH. Therefore, the present results support the notion that FO may have therapeutic utility in treating learning/memory dysfunction after acute/transient cerebral ischemia and suggest that such benefits may not apply when a state of chronic cerebrovascular insufficiency is present.

Glucocorticoids aggravate retrograde memory deficiency associated with traumatic brain injury in rats.

Administration of glucocorticoid to patients with head injury has previously been demonstrated to impair memory. We hypothesize that glucocorticoids promote post-traumatic hippocampal apoptosis, resulting in retrograde memory deficiency associated with traumatic brain injury (TBI). In the present study, we tested this hypothesis by measuring spatial memory deficiency in rats subjected to fluid percussion injury (FPI) and receiving dexamethasone (DXM at 0.5-10 mg/kg) or methylprednisolone (MP at 5-30 mg/kg); we also examined neuronal apoptosis in hippocampus. Adult male Wistar rats were trained for the acquisition of spatial memory, then subjected to FPI and tested for spatial reference memory on post-injury days 7 and 14 using the Morris Water Maze. Brain tissue from injured rats was examined 24 h to 2 weeks after injury. The percent time in the goal quadrant, which measures spatial reference memory, was significantly lower in injured rats receiving either high-dose DXM or MP than in control groups. TUNEL-positive cells in hippocampus were first detected 24 h post-injury, plateauing at 48h. The number of TUNEL-positive cells was significantly higher in injured rats treated with either DXM or MP. The data suggest that glucocorticoid therapy for TBI may increase neuronal apoptosis in hippocampus and, as a result, aggravate retrograde memory deficits induced by TBI.

Injury and recovery: severe amnestic syndrome following traumatic brain injury.

PRIMARY OBJECTIVE: To illustrate the clinical course of a patient with a marked amnestic syndrome resulting from a closed head injury that had significant effects on frontal and thalamic memory structures. METHODS AND PROCEDURES: The patient underwent a series of brain imaging investigations (CT and MRI) and neuropsychological investigations to determine the severity and course of behavioural and cognitive impairments. RESULTS: Three months post-injury, the patient demonstrated dense retrograde and anterograde amnesia for auditory-verbal and visuo-spatial information, disorientation and confabulation. In contrast, memory for faces appeared unimpaired. One month later the patient's behaviour, orientation and spatial memory had improved with no concomitant improvement in auditory-verbal memory. CONCLUSIONS: The findings indicate that injury to the diencephalon manifests in a verbal amnesic syndrome that is anterograde in nature if localized in the region of the anterior left thalamus, but leaves a relatively intact visual memory. Furthermore, injuries to the frontal and temporal lobes and their projections to the diencephalon may be more important in the emergence and resolution of retrograde amnesia and disturbances in autobiographical recall than previously appreciated.

Two routes to losing one's past life: a brain trauma, an emotional trauma.

Organic and psychogenic retrograde amnesia have long been considered as distinct entities and as such, studied separately. However, patterns of neuropsychological impairments in organic and psychogenic amnesia can bear interesting resemblances despite different aetiologies. In this paper, two cases with profound, selective and permanent retrograde amnesia are presented, one of an apparent organic origin and the other with an apparent psychogenic cause. The first case, DD, lost his memory after focal brain injury from a nail gun to the right temporal lobe. The second case, AC, lost her memory in the context of intense psychological suffering. In both cases, pre-morbid autobiographical memory for people, places and events was lost, and no feeling of familiarity was experienced during relearning. In addition, they both lost some semantic knowledge acquired prior to the onset of the amnesia. This contrasts with the preservation of complex motor skills without any awareness of having learned them. Both DD and AC showed mild deficits on memory tests but neither presented any anterograde amnesia. The paradox of these cases--opposite causes yet similar clinical profile--exemplifies the hypothesis that organic and psychogenic amnesia may be two expressions of the same faulty mechanism in the neural circuitry.

Hyperbaric oxygen therapy in orthopedic conditions: an evaluation of safety.

BACKGROUND: Because of the documented cellular and biochemical benefits of hyperbaric oxygen (HBO), HBO therapy is applied now with increasing frequency to various orthopedic conditions. Many traumatologists and orthopedic surgeons might refer their patients for adjuvant HBO therapy. However, the potential risks and risk-benefit ratio have often been underemphasized in therapeutic trials. METHODS: From October 2002 to September 2004, 240 patients with a total of 4,638 treatments received HBO therapy at the hyperbaric medicine center of our institution on an identical treatment protocol. HBO therapy patient treatment logs were reviewed to analyze the incidence of complications during HBO treatment. RESULTS: The overall incidence of complications was 1.83%. Over 94% of treatment complications were mild to moderate and designated as minor complications; fewer than 6% were severe or life threatening and designated as major complications. The incidence of major complications (central nervous system [CNS] oxygen toxicity in this series) was 0.109%. There was no mortality. Two patients with unusual presentation of CNS oxygen toxicity were observed during the study period. CONCLUSIONS: HBO therapy in orthopedic conditions is considered as a safe treatment because of a very low complication rate; however, analysis of patients with CNS oxygen toxicity revealed its unpredictability and inevitability. Although it is common sense that patients who develop a seizure in the hospital need help from the medical staff, it cannot be done in a monoplace hyperbaric chamber because of pressure unequalization. Therefore, a multiplace chamber equipped with an antechamber for medical contingency is possibly the better facility in consideration of safety.

[Dementia secondary to thalamic infarct: a case report]. / Demencia secundaria a infarto talamico: comunicacion de un caso.

INTRODUCTION: The term dementia refers to the deterioration of the intellectual or cognitive functions, with little or no alteration of consciousness, which is capable of interfering with the activities of daily living and the ability to cope by oneself. One infrequent cause of dementia is its being secondary to a thalamic lesion and is normally due to the involvement of both thalami. CASE REPORT: We report a case of sudden onset dementia caused by lesions affecting only the left thalamus. A 64 year old right handed female patient with chronic arterial hypertension for which she received regular treatment. The patient visited because of difficulty in speaking without any alterations to consciousness, and amnesia of recent anterograde and retrograde events. A CAT scan of the brain revealed a superlacuna in the left thalamus. From then on, the patient presented memory disorders, the most typical being loss of retention memory. CONCLUSIONS: Thalamus injuries that are accompanied by dementia are commonly bilateral and are preferably located in the anterior and medial nuclei. There have been cases of memory disorders secondary to unilateral infarcts of the thalamus and these are related to a thalamocortical deafferentiation. Our case is one of sudden onset thalamic dementia secondary to an infarct affecting only the left thalamus.

Herbal pharmacotherapy for the attenuation of electroconvulsive shock-induced anterograde and retrograde amnestic deficits.

BR-16A is an herbal (non-allopathic) medication used in India to enhance cognition. Sixty adult male Sprague Dawley rats received either BR-16A (200 mg/kg/day) or vehicle alone for 16 days. During the first 7 days, the rats were trained in a spatial memory task using the Hebb Williams complex maze. Once a day for the next 2 days, rats in BR-16A and control groups received either true or sham electroconvulsive shock (ECS). During the last 7 days of the study, the rats were reexposed to the maze to assess recall of pre-ECS training and to evaluate further improvement in learning scores. BR-16A-treated rats performed better than controls both before and after ECS. It is concluded that BR-16A facilitates learning and that this effect extends to a protection against ECS-induced anterograde and retrograde amnesia. BR-16A may hence hold promise in the restriction of ECT-induced cognitive compromise. An unexpected observation in this study was that BR-16A attenuated seizure duration; implications and mechanisms are discussed.

Recall of informed consent after endoscopic procedures.

PURPOSE: The aim of this study was to determine if recall of informed consent is affected by the timing of obtaining informed consent before endoscopic procedures. METHODS: Sixty patients scheduled for colonoscopy or esophagogastroduodenoscopy were enrolled in this prospective, randomized study. Each patient received informed consent 24 to 72 hours or immediately before the procedure, and follow-up occurred one to three days postprocedure. RESULTS: There was no statistically significant difference in recall of informed consent or the individual elements of informed consent (indication, risks, benefits, alternatives) between the two groups. CONCLUSION: Recall of informed consent is similar whether consent is obtained immediately or several days before endoscopic procedures.

ECT-induced anterograde amnesia: can the deficits be minimized?

To date, no pharmacological agent has been confirmed to lessen electroconvulsive therapy (ECT)-induced memory deficits. BR-16A is an herbal preparation, containing various organic extracts, used in India for the enhancement of cognition (among other applications). In the present study, adult male Sprague-Dawley rats received six once-daily electroconvulsive shocks (ECSs). Half the animals were treated with BR-16A (200 mg/kg/day) for 1 week before ECS, during the ECS course, and during the post-ECS learning assessment phase; the remaining animals received vehicle alone. In experiment 1, rats (n = 16/treatment group) were preassessed for learning on days 3 and 5 of exposure to the Hebb-Williams complex maze and were reassessed after comparable exposure to the maze starting from the second day post-ECS. In experiment 2, rats (n = 9/treatment group) were preassessed for number of trials to satisfactory learning and number of wrong arm entries in a T-maze and were reassessed on the second day post-ECS. The learning preassessments were conducted just prior to the commencement of the BR-16A/vehicle treatments. In both experiments, rats receiving BR-16A performed significantly better than controls. It is concluded that BR-16A protects against ECS-induced anterograde amnesia. BR-16A may therefore have scope in minimizing ECT-induced learning deficits.

[A comparative study of the nootropic properties of piracetam and oxiracetam]. / Sravnitel'noe izuchenie nootropnykh svoistv piratsetama i oksiratsetama,

The behavioral activities of piracetam and oxiracetam were studied during the learning tests (active avoidance, passive avoidance, T-maize). The levels of the orientation reaction and emotionality of the animals were determined by the "open field" method. To achieve similar effects, injections of 10 mg/kg of oxiracetam and 100 mg/kg of piracetam intraperitoneally were required. Both nootropics facilitated the learning of the animals but failed to change their behavior in the open field. Piracetam was more effective in the active avoidance test and oxiracetam in the T-maize test. The data indicate some differences in the activities of piracetam and oxiracetam.

[Comparative influence of nootropic preparations on the emetic effect of morphine]. / Sravnitel'noe vliianie nootropnykh preparatov na émeticheskii éffekt morfina.

The effect of electroshock (ECS) and piracetam, oxiracetam or N-acetylglycinamide on the passive avoidance conditioned response in rats was studied. The antiemetic effect of the compounds was examined in cats as well. The results obtained allowed us to distinct the nootropic and antiemetic action of the drugs. The substances possessed a similar ability to prevent ECS-induced amnesia. On the contrary, oxiracetam completely prevented the emetic response to morphine at doses 100 times lower and piracetam at doses 10 times higher then those of the opioid. N-Acetylglycinamide had no antiemetic activity. The results obtained show that oxiracetam is 100 times more active in antiemetic test than piracetam. These data comprise the novel properties of nootropic drugs.