Long-term Cognitive Changes Research Articles

Long-term behavioral effects observed in mice chronically exposed to static ultra-high magnetic fields.

The primary goal of this study was to investigate whether chronic exposures to ultra-high B0 fields can induce long-term cognitive, behavioral, or biological changes in C57BL/6 mice. C57BL/6 mice were chronically exposed to 10.5-T or 16.4-T magnetic fields (3-h exposures, two exposure sessions per week, 4 or 8 weeks of exposure). In vivo single-voxel 1 H magnetic resonance spectroscopy was used to investigate possible neurochemical changes in the hippocampus. In addition, a battery of behavioral tests, including the Morris water-maze, balance-beam, rotarod, and fear-conditioning tests, were used to examine long-term changes induced by B0 exposures. Hippocampal neurochemical profile, cognitive, and basic motor functions were not impaired by chronic magnetic field exposures. However, the balance-beam-walking test and the Morris water-maze testing revealed B0 -induced changes in motor coordination and balance. The tight-circling locomotor behavior during Morris water-maze tests was found as the most sensitive factor indexing B0 -induced changes. Long-term behavioral changes were observed days or even weeks subsequent to the last B0 exposure at 16.4 T but not at 10.5 T. Fast motion of mice in and out of the 16.4-T magnet was not sufficient to induce such changes. Observed results suggest that the chronic exposure to a magnetic field as high as 16.4 T may result in long-term impairment of the vestibular system in mice. Although observation of mice may not directly translate to humans, nevertheless, they indicate that studies focused on human safety at very high magnetic fields are necessary.

Poor lung function accelerates cognitive decline in middle-aged and older adults: Evidence from the English Longitudinal Study of Ageing

Background/objectivePrevious studies have linked lung function to cognitive performance. However, it is not clear whether baseline lung function has an effect on the trajectory of cognitive decline during normal aging. This study aimed to examine the association of baseline lung function with long-term changes in cognition among the middle-aged and older adults. MethodsLung function as indicated by forced expiratory volume 1 s (FEV1) and forced vital capacity (FVC), was measured at the baseline examination. Cognition, including memory, time orientation, executive function and processing speed, were tested four times over six years. Generalized estimating equation (GEE) models were used to test the associations between baseline lung function and four visits of cognition in 6080 participants aged 50 years or over from the English Longitudinal Study of Ageing (ELSA). ResultsCompared to participants with higher lung function, those who had lower lung function at baseline experienced a faster rate of decline in memory (joint test: χ2interaction = 12.07, df = 3, P = 0.007 for FVC), time orientation (joint test: χ2interaction = 9.49, df = 3, P = 0.023 for FVC) and executive function (joint test: χ2interaction = 9.13, df = 3, P = 0.028 for FEV1 and joint test: χ2interaction = 12.76, df = 3, P = 0.005 for FVC). No association was found between baseline lung function and the rate of decline in processing speed (joint test: χ2interaction = 1.29, df = 3, P=0.733 for FEV1 and joint test: χ2interaction = 2.35, df = 3, P = 0.503 for FVC). ConclusionsPoor lung function at baseline predicted a faster rate of cognitive decline in memory, time orientation and executive function. The mechanism for this association deserves further investigation.

Long-term alterations in brain and behavior after postnatal Zika virus infection in infant macaques

Zika virus (ZIKV) infection has a profound impact on the fetal nervous system. The postnatal period is also a time of rapid brain growth, and it is important to understand the potential neurobehavioral consequences of ZIKV infection during infancy. Here we show that postnatal ZIKV infection in a rhesus macaque model resulted in long-term behavioral, motor, and cognitive changes, including increased emotional reactivity, decreased social contact, loss of balance, and deficits in visual recognition memory at one year of age. Structural and functional MRI showed that ZIKV-infected infant rhesus macaques had persistent enlargement of lateral ventricles, smaller volumes and altered functional connectivity between brain areas important for socioemotional behavior, cognitive, and motor function (e.g. amygdala, hippocampus, cerebellum). Neuropathological changes corresponded with neuroimaging results and were consistent with the behavioral and memory deficits. Overall, this study demonstrates that postnatal ZIKV infection in this model may have long-lasting neurodevelopmental consequences.

Parity is associated with cognitive function and brain age in both females and males

Previous studies of the association between parity and long-term cognitive changes have primarily focused on women and have shown conflicting results. We investigated this association by analyzing data collected on 303,196 subjects from the UK Biobank. We found that in both females and males, having offspring was associated with a faster response time and fewer mistakes made in the visual memory task. Subjects with two or three children had the largest differences relative to those who were childless, with greater effects observed in men. We further analyzed the association between parity and relative brain age (n = 13,584), a brain image-based biomarker indicating how old one’s brain structure appears relative to peers. We found that in both sexes, subjects with two or three offspring had significantly reduced brain age compared to those without offspring, corroborating our cognitive function results. Our findings suggest that lifestyle factors accompanying having offspring, rather than the physical process of pregnancy experienced only by females, contribute to these associations and underscore the importance of studying such factors, particularly in the context of sex.

Patient risk factors associated with embolic stroke volumes after revascularization

ObjectivePrevious research has shown that subclinical, microembolic infarcts result in long-term cognitive changes. Whereas both carotid endarterectomy (CEA) and carotid artery stenting (CAS) have potential for microembolic events, CAS has been shown to have a larger volume of infarct. We have previously shown that large-volume infarction is associated with long-term memory deterioration. The purpose of this study was to identify independent risk factors that trend toward higher embolic volumes in both procedures. MethodsA total of 162 patients who underwent carotid revascularization procedures were prospectively recruited at two separate institutions. Preoperative and postoperative brain magnetic resonance images were compared to identify procedure-related microinfarcts. A novel semiautomated approach was used to define volumes of infarcts for each patient. Patient-related factors including comorbidities, symptomatic status, and medications were analyzed. Tweedie regression analysis was used to identify risk factors associated with procedure-related infarct volume. Variables with an unadjusted P value of ≤ .05 were included in the multivariate analysis. ResultsThere were 80 CAS and 82 CEA procedures performed and analyzed for the data set; 81% of CAS patients had procedure-related new infarcts with a mean volume of 388.15 ± 927.90 mm3 compared with 30% of CEA patients with a mean volume of 74.80 ± 225.52 mm3. In the CAS cohort, increasing age (adjusted coefficient ± standard error, 0.06 ± 0.02; P < .01) and obesity (1.14 ± 0.35; P < .01) were positively correlated with infarct volume, whereas antiplatelet use (−1.11 ± 0.33; P < .001) was negatively correlated with infarct volume. For the CEA group, diabetes (adjusted coefficient ± standard error, 1.69 ± 0.65; P < .01) was identified as the only risk factor positively correlated with infarct volume, whereas increasing age (−0.10 ± 0.05; P = .03) was negatively correlated with infarct volume. ConclusionsRisk factors for CAS- or CEA-related infarct volumes are identified in our study. Although the result warrants further validation, this study showed that advanced age, obesity, and diabetes independently predicted volume of microinfarcts related to CAS and CEA. These data provide valuable information for patient factor-based risk stratification and preoperative consultation for each procedure.

Male mice placed on a ketogenic diet from postnatal day (P) 21 through adulthood have reduced growth, are hypoactive, show increased freezing in a conditioned fear paradigm, and have spatial learning deficits

The ketogenic diet (KD) is a non-pharmacological treatment for specific types of epilepsy. In addition, it has been shown to be effective in mitigating other neurologic disorders. The KD is also effective in reducing body mass, leading to an increase in use by the general population for weight loss. As the popularity of the clinical and general use of the KD has increased, it is important to develop adequate mouse models to better understand the effects of the KD in both normal and diseased states. Many times, the best outcome for disorders treatable with the KD would be achieved by commencing treatment in early life. Few studies have evaluated the cognitive effect of starting the KD in early life. To better understand these effects, male C57BL6/J mice were placed on a KD from postnatal day (P) 21 through young adulthood (~P90). KD-fed mice had increased blood ketone levels, reduced blood glucose, and reduced weight gain versus mice fed a control diet (CD). The weight loss in the KD-fed mice was not accompanied by a change in body fat percentage, suggesting that there was a loss of lean mass. Behavioral testing began on P60 while the mice were still on the diet. KD-fed mice were hypoactive with CD-fed mice. In the Morris water maze, KD-fed mice showed decreased path efficiency, suggesting a spatial learning deficits. No differences were observed in spatial memory or in novel object recognition memory. In a contextual and conditioned fear paradigm, the KD-fed mice had an increase in freezing behavior. These data suggest that early-life exposure to a KD leads to impaired body composition and long-term cognitive changes.

Novel imaging technologies for genetic diagnoses in the inborn errors of metabolism.

Many inborn errors of metabolism and genetic disorders affect the brain. The brain biochemistry may differ from that in the periphery and is not accessible by simple blood and urine sampling. Therefore, neuroimaging has proven to be a valuable tool to not only evaluate the brain structure, but also biochemistry, blood flow and function. Neuroimaging in patients with inborn errors of metabolism can include additional sequences in addition to T1 and T2-weighted imaging because in early stages, there may be no significant findings on the routine sequnces due to the lack of sensitivity or the evolution of abnormalities lags behind the ability of the imaging to detect it. In addition, findings on T1 and T2-weighted imaging of several inborn errors of metabolism may be non-specific and be seen in other non-genetic conditions. Therefore, additional neuroimaging modalities that have been employed including diffusion tensor imaging (DTI), magnetic resonance spectroscopy, functional MRI (fMRI), functional near infrared spectroscopy (fNIRS), or positron emission tomography (PET) imaging may further inform underlying changes in myelination, biochemistry, and functional connectivity. The use of Magnetic Resonance Spectroscopy in certain disorders may add a level of specificity depending upon the metabolite levels that are abnormal, as well as provide information about the process of brain injury (i.e., white matter, gray matter, energy deficiency, toxic buildup or depletion of key metabolites). It is even more challenging to understand how genetic or metabolic disorders contribute to short and/or long term changes in cognition which represent the downstream effects of IEMs. In order to image “cognition” or the downstream effects of a metabolic disorder on domains of brain function, more advanced techniques are required to analyze underlying fiber tracts or alternatively, methods such as fMRI enable generation of brain activation maps after both task based and resting state conditions. DTI can be used to look at changes in white matter tracks. Each imaging modality can explore an important aspect of the anatomy, physiology or biochemisty of the central nervous system. Their properties, pros and cons are discussed in this article. These imaging modalities will be discussed in the context of several inborn errors of metabolism including Galactosemia, Phenylketonruia, Maple syrup urine disease, Methylmalonic acidemia, Niemann-Pick Disease, type C1, Krabbe Disease, Ornithine transcarbamylase deficiency, Sjogren Larsson syndrome, Pelizeaus-Merzbacher disease, Pyruvate dehydrogenase deficiency, Nonketotic Hyperglycinemia and Fabry disease. Space constraints do not allow mention of all the disorders in which one of these modalities has been investigated, or where it would add value to diagnosis or disease progression.

Long-term Changes in Cognitive Functioning in Individuals With Psychotic Disorders

It remains uncertain whether people with psychotic disorders experience progressive cognitive decline or normal cognitive aging after first hospitalization. This information is essential for prognostication in clinical settings, deployment of cognitive remediation, and public health policy. To examine long-term cognitive changes in individuals with psychotic disorders and to compare age-related differences in cognitive performance between people with psychotic disorders and matched control individuals (ie, individuals who had never had psychotic disorders). The Suffolk County Mental Health Project is an inception cohort study of first-admission patients with psychosis. Cognitive functioning was assessed 2 and 20 years later. Patients were recruited from the 12 inpatient facilities of Suffolk County, New York. At year 20, the control group was recruited by random digit dialing and matched to the clinical cohort on zip code and demographics. Data were collected between September 1991 and July 2015. Analysis began January 2016. Change in cognitive functioning in 6 domains: verbal knowledge (Wechsler Adult Intelligence Scale-Revised vocabulary test), verbal declarative memory (Verbal Paired Associates test I and II), visual declarative memory (Visual Reproduction test I and II), attention and processing speed (Symbol Digit Modalities Test-written and oral; Trail Making Test [TMT]-A), abstraction-executive function (Trenerry Stroop Color Word Test; TMT-B), and verbal fluency (Controlled Oral Word Association Test). A total of 705 participants were included in the analyses (mean [SD] age at year 20, 49.4 [10.1] years): 445 individuals (63.1%) had psychotic disorders (211 with schizophrenia spectrum [138 (65%) male]; 164 with affective psychoses [76 (46%) male]; 70 with other psychoses [43 (61%) male]); and 260 individuals (36.9%) in the control group (50.5 [9.0] years; 134 [51.5%] male). Cognition in individuals with a psychotic disorder declined on all but 2 tests (average decline: d = 0.31; range, 0.17-0.54; all P < .001). Cognitive declines were associated with worsening vocational functioning (Visual Reproduction test II: r = 0.20; Symbol Digit Modalities Test-written: r = 0.25; Stroop: r = 0.24; P < .009) and worsening negative symptoms (avolition: Symbol Digit Modalities Test-written: r = -0.24; TMT-A: r = -0.21; Stroop: r = -0.21; all P < .009; inexpressivity: Stroop: r = -0.22; P < .009). Compared with control individuals, people with psychotic disrders showed age-dependent deficits in verbal knowledge, fluency, and abstraction-executive function (vocabulary: β = -0.32; Controlled Oral Word Association Test: β = -0.32; TMT-B: β = 0.23; all P < .05), with the largest gap among participants 50 years or older. In individuals with psychotic disorders, most cognitive functions declined over 2 decades after first hospitalization. Observed declines were clinically significant. Some declines were larger than expected due to normal aging, suggesting that cognitive aging in some domains may be accelerated in this population. If confirmed, these findings would highlight cognition as an important target for research and treatment during later phases of psychotic illness.

Traumatic brain injury-related hospitalizations and deaths among American Indians and Alaska natives — United States, 2008–2014

IntroductionDespite progress, injury remains the leading cause of preventable death for American Indian and Alaska Natives (AI/AN), aged 1 to 44. There are few publications on injuries among the AI/AN population, especially those on traumatic brain injury (TBI). A TBI can cause short- or long-term changes in cognition, communication, and/or emotion. Methods: To describe changes over time in TBI incidence by mechanism of injury, injury intent, and age group among AI/ANs, the CDC analyzed hospitalization and death data from the 2008–2014 Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS) and the National Vital Statistics System (NVSS), respectively. Results: From 2008-2014, the incidence of TBI-related hospitalizations increased by 32% (1,477 in 2008 to 1,945 in 2014) and resulted in a 21% increase in age-adjusted rates of people hospitalized with TBI. TBI-related deaths increased in number (569 in 2008 to 644 in 2014) and age-adjusted rate (22.7 in 2008 to 25.4 in 2014) by approximately 13% and 12%, respectively. Motor-vehicle crashes were the leading cause of TBI-related deaths among AI/ANs aged 0–54 years. Practical application: Prevention efforts should focus on increasing motor-vehicle safety and advancing prevention strategies for other leading causes of TBI, including: falls, intentional self-harm, and assaults.

Frequency and risk factors associated with post-stroke dementia-an observational study on stroke patients without premorbid cognitive impairment

Longitudinal studies on cognitive outcomes after stroke revealed heterogeneous results and the underlying pathology and risk factors for so-called post-stroke dementia are unclear. To assess long-term cognitive performance changes in patients after the first ischemic stroke and to evaluate possible risk factors for post-stroke dementia. In this study 66 clinically mildly affected patients aged 54-87years without ahistory of dementia underwent extensive neuropsychological assessment after first ever ischemic stroke and again 6 months after the event (follow-up assessment). Demographic, clinical and paraclinical parameters were assessed as potential predictors for long-term cognitive outcome. At the group level significant performance improvements were found for most of the neurocognitive domains at the follow-up assessment. The greatest cognitive improvement was found in visuospatial processing. Immediately after stroke 54.5% of patients were considered cognitively impaired (z-scores < -2 in at least 2 neurocognitive domains). At follow-up only 16.7% were considered cognitively impaired according to this criterion and among these only 2 patients (3%) had developed anew, clinically relevant cognitive impairment (i.e. post-stroke dementia). Patients with inferior cognitive performance improvements at follow-up had on average larger brain lesions caused by the stroke as well as aprediabetic metabolic status. The probability of developing apost-stroke dementia syndrome is lower than previously assumed in patients with first ever stroke, with only mild clinical disability and without premorbid cognitive impairment. Long-term cognitive impairment could primarily be determined by the size of the lesioned brain area as well as the premorbid (pre)diabetic status.

Successes and shortcomings of climate change communication: insights from a longitudinal analysis of Swedish Forest owners

Communication is a popular method to raise awareness and promote action against the impacts of climate change. However, there is little scientific evidence that climate change communication can influence individual engagement with adaptation. This study combines qualitative and quantitative data to assess long-term cognitive and behavioral changes among Swedish forest owners who took part in climate change communication. Overall, the results suggest that climate change communication has only limited direct effect on individual engagement with adaptation. While the data show that climate change communication can have strengthened forest owners’ perceived knowledgeability and belief in climate change, they had also become less concerned about climate change risks and did not change how they managed their forest. The study concludes that researchers and practitioners should learn how to better tailor climate change communication to the personal experiences and decision-making needs of their target audience and involve trusted peers and information channels.

A single inhalation of vapor from dried toad secretion containing 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) in a naturalistic setting is related to sustained enhancement of satisfaction with life, mindfulness-related capacities, and a decrement of psychopathological symptoms

Background5-methoxy-N,N-dimethyltryptamine (hereinafter referred to as 5-MeO-DMT) is a psychedelic substance found in the secretion from the parotoid glands of the Bufo alvarius toad. Inhalation of vapor from toad secretion containing 5-MeO-DMT has become popular in naturalistic settings as a treatment of mental health problems or as a means for spiritual exploration. However, knowledge of the effects of 5-MeO-DMT in humans is limited.AimsThe first objective of this study was to assess sub-acute and long-term effects of inhaling vapor from dried toad secretion containing 5-MeO-DMT on affect and cognition. The second objective was to assess whether any changes were associated with the psychedelic experience.MethodsAssessments at baseline, within 24 h and 4 weeks following intake, were made in 42 individuals who inhaled vapor from dried toad secretion at several European locations.ResultsRelative to baseline, ratings of satisfaction with life and convergent thinking significantly increased right after intake and were maintained at follow-up 4 weeks later. Ratings of mindfulness also increased over time and reached statistical significance at 4 weeks. Ratings of depression, anxiety, and stress decreased after the session, and reached significance at 4 weeks. Participants that experienced high levels of ego dissolution or oceanic boundlessness during the session displayed higher ratings of satisfaction with life and lower ratings of depression and stress.ConclusionA single inhalation of vapor from dried toad secretion containing 5-MeO-DMT produces sub-acute and long-term changes in affect and cognition in volunteers. These results warrant exploratory research into therapeutic applications of 5-MeO-DMT.

Long-Term Cognitive and Psychological Functioning in Post-Electroconvulsive Therapy Patients.

Electroconvulsive therapy (ECT) is associated with positive outcomes for treatment-resistant mood disorders in the short term. However, there is limited research on long-term cognitive or psychological changes beyond 1 year after -ECT. This study evaluated long-term outcomes in cognitive functioning, psychiatric symptoms, and quality of life for individuals who had undergone ECT. Eligible participants (N = 294) who completed a brief pre-ECT neuropsychological assessment within the last 14 years were recruited for a follow-up evaluation; a limited sample agreed to follow-up testing (n = 34). At follow-up, participants were administered cognitive measures (Repeatable Battery for the Assessment of Neuropsychological Status [RBANS], Wide Range Achievement Test-4 Word Reading, Trail Making Test, Wechsler Adult Intelligence Scale-Fourth Edition Letter Number Sequence and Digit Span, and Controlled Oral Word Association Test), along with emotional functioning measures (Beck Depression Inventory-Second Edition [BDI-II] and Beck Anxiety Inventory) and the World Health Organization Quality of Life-BREF quality of life measure. Follow-up-testing occurred on average (SD) 6.01 (3.5) years after last ECT treatment. At follow-up, a paired t test showed a large and robust reduction in mean BDI-II score. Scores in cognitive domains remained largely unchanged. A trend was observed for a mean reduction in RBANS visual spatial scores. Lower BDI-II scores were significantly associated with higher RBANS scores and improved quality of life. For some ECT patients, memory, cognitive functioning, and decreases in depressive symptoms can remain intact and stable even several years after ECT. However, the selective sampling at follow-up makes these results difficult to generalize to all post-ECT patients. Future research should examine what variables may predict stable cognitive functioning and a decline in psychiatric symptoms after ECT.

Long-Term Changes in Cognition and Physiology after Low-Dose 16O Irradiation.

Astronauts traveling to Mars will be exposed to high levels of ionizing radiation upon leaving low-Earth orbit. During prolonged space travel, astronauts are exposed to galactic cosmic rays (GCRs) composed of protons; oxygen molecules; and high energy, high mass charged particles. Notably, oxygen molecules can travel through the shielding of spacecraft, potentially impacting 25% of the hippocampus. The aim of the current study was to assess whether 16O-particle radiation induced a behavioral deficit and histological changes in mice. Mice were sent to the National Aeronautics and Space Administration (NASA) Space Radiation Laboratory at Brookhaven National Laboratory and exposed to particulate 16O radiation at doses of 0 and 0.05 Gy. Nine months after irradiation, the mice were tested for novel object recognition and in the Y-maze, after which the animals were sacrificed. The brains were then dissected along the midsagittal plane for Golgi staining. Exposure to 0.05 Gy significantly impaired novel object recognition. However, short term memory and exploratory activity in the Y-maze were not affected. Micromorphometric analysis revealed significant decreases in mushroom spine density in the dentate gyrus and cornu Ammonis-1 and -3 of the hippocampus. Sholl analysis revealed a significant decrease in dendritic complexity in the dentate gyrus. The present data provide evidence that space radiation has deleterious effects on mature neurons associated with hippocampal learning and memory.

Corrigendum: Chronic MK-801 Application in Adolescence and Early Adulthood: A Spatial Working Memory Deficit in Adult Long-Evans Rats But No Changes in the Hippocampal NMDA Receptor Subunits

[This corrects the article on p. 42 in vol. 9, PMID: 29487522.].

Chronic MK-801 Application in Adolescence and Early Adulthood: A Spatial Working Memory Deficit in Adult Long-Evans Rats But No Changes in the Hippocampal NMDA Receptor Subunits

The role of NMDA receptors in learning, memory and hippocampal function has long been recognized. Post-mortem studies have indicated that the expression or subunit composition of the NMDA glutamate receptor subtype might be related to the impaired cognitive functions found in schizophrenia patients. NMDA receptor antagonists have been used to develop animal models of this disorder. There is accumulating evidence showing that not only the acute but also the chronic application of NMDA receptor antagonists may induce schizophrenia-like alterations in behavior and brain functions. However, limited evidence is available regarding the consequences of NMDA receptor blockage during periods of adolescence and early adulthood. This study tested the hypothesis that a 2-week treatment of male Long-Evans and Wistar rats with dizocilpine (MK-801; 0.5 mg/kg daily) starting at postnatal days (PD) 30 and 60 would cause a long-term cognitive deficit and changes in the levels of NMDA receptor subunits. The working memory version of the Morris water maze (MWM) and active place avoidance with reversal on a rotating arena (Carousel) requiring cognitive coordination and flexibility probed cognitive functions and an elevated-plus maze (EPM) was used to measure anxiety-like behavior. The western blot method was used to determine changes in NMDA receptor subunit levels in the hippocampus. Our results showed no significant changes in behaviors in Wistar rats. Slightly elevated anxiety-like behavior was observed in the EPM in Long-Evans rats with the onset of treatment on PD 30. Furthermore, Long-Evans rats treated from PD 60 displayed impaired working memory in the MWM. There were; however, no significant changes in the levels of NMDA receptor subunits because of MK-801 administration. These findings suggest that a 2-week treatment starting on PD 60 in Long-Evans rats leads to long-term changes in working memory, but this deficit is not paralleled by changes in NMDA receptor subunits. These results support the face validity, but not construct validity of this model. We suggest that chronic treatment of adolescent and adult rats does not constitute a plausible animal model of schizophrenia.

Cognitive Deficits after Cerebral Ischemia and Underlying Dysfunctional Plasticity: Potential Targets for Recovery of Cognition.

Cerebral ischemia affects millions of people worldwide and survivors suffer from long-term functional and cognitive deficits. While stroke and cardiac arrest are typically considered when discussing ischemic brain injuries, there is much evidence that smaller ischemic insults underlie neurodegenerative diseases, including Alzheimer's disease. The "regenerative" capacity of the brain relies on several aspects of plasticity that are crucial for normal functioning; less affected brain areas may take over function previously performed by irreversibly damaged tissue. To harness the endogenous plasticity mechanisms of the brain to provide recovery of cognitive function, we must first understand how these mechanisms are altered after damage, such as cerebral ischemia. In this review, we discuss the long-term cognitive changes that result after cerebral ischemia and how ischemia alters several plasticity processes. We conclude with a discussion of how current and prospective therapies may restore brain plasticity and allow for recovery of cognitive function, which may be applicable to several disorders that have a disruption of cognitive processing, including traumatic brain injury and Alzheimer's disease.

Models used in the study of traumatic brain injury

Traumatic brain injury (TBI) is a contemporary health problem and a leading cause of mortality and morbidity worldwide. Survivors of TBI frequently experience disabling long-term changes in cognition, sensorimotor function, and personality. A crucial step in understanding TBI and providing better treatment has been the use of models to mimic the event under controlled conditions. Here, we describe the known head injury models, which can be classified as whole animal (in vivo), in vitro, and mathematical models. We will also review the ways in which these models have advanced the knowledge of TBI.

Relationship between radiation dose and microbleed formation in patients with malignant glioma

BackgroundCranial irradiation is associated with long-term cognitive changes. Cerebral microbleeds (CMBs) have been identified on susceptibility-weighted MRI (SWI) in patients who have received prior cranial radiation, and serve as radiographic markers for microvascular injury thought to contribute to late cognitive decline. The relationship between CMB formation and radiation dose has not previously been quantified.MethodsSWI was performed on 13 patients with stable WHO grade III-IV gliomas between 2 and 4 years after chemoradiotherapy to 60 Gy. The median age at the time of treatment was 41 years (range 25 – 74 years). CMBs were identified as discrete foci of susceptibility on SWI that did not correspond to vessels. CMB density for low (<30 Gy), median (30–45 Gy), and high (>45 Gy) dose regions was computed.ResultsTwelve of 13 patients exhibited CMBs. The number of CMBs was significantly higher for late (>3 years from treatment) compared to early (<3 years) timepoints (early median 6 CMBs; late median 27 CMBs; p = 0.001), and there were proportionally more CMBs at lower doses for late scans (p = 0.006). 88% of all CMBs were observed in regions receiving at least 30 Gy, but the CMB density within medium and high dose regions was not significantly different (p = 0.33 and p = 0.9, respectively, for early and late time points).ConclusionsCMBs predominantly form in regions receiving at least 30 Gy, but form in lower dose regions with longer follow-up. We do not observe a clear dose–response relationship at doses above 30 Gy. These findings provide important information to assess the risk of late microvascular sequelae from cranial irradiation.

Mild and Mild-to-Moderate Traumatic Brain Injury-Induced Significant Progressive and Enduring Multiple Comorbidities.

Traumatic brain injury (TBI) can produce life-long disabilities, including anxiety, cognitive, balance, and motor deficits. The experimental model of closed head TBI (cTBI) induced by weight drop/impact acceleration is known to produce hallmark TBI injuries. However, comprehensive long-term characterization of comorbidities induced by graded mild-to- mild/moderate intensities using this experimental cTBI model has not been reported. The present study used two intensities of weight drop (1.0 m and 1.25 m/450 g) to produce cTBI in a rat model to investigate initial and long-term disability of four comorbidities: anxiety, cognitive, vestibulomotor, and spinal reflex that related to spasticity. TBI and sham injuries were produced under general anesthesia. Time for righting recoveries post-TBI recorded to estimate duration of unconsciousness, revealed that the TBI mild/moderate group required a mean of 1 min 27 sec longer than the values observed for noninjured sham animals. Screening magnetic resonance imaging images revealed no anatomical changes, mid-line shifts, or hemorrhagic volumes. However, compared to sham injuries, significant long-term anxiety, cognitive, balance, and physiological changes in motor reflex related to spasticity were observed post-TBI for both TBI intensities. The longitudinal trajectory of anxiety and balance disabilities tested at 2, 4, 8, and 18 weeks revealed progressively worsening disabilities. In general, disability magnitudes were proportional to injury intensity for three of the four measures. A natural hypothesis would pose that all disabilities would increase incrementally relative to injury severity. Surprisingly, anxiety disability progressed over time to be greater in the mildest injury. Collectively, translational implications of these observations suggest that patients with mild TBI should be evaluated longitudinally at multiple time points, and that anxiety disorder could potentially have a particularly low threshold for appearance and progressively worsen post-injury.