Focal Ischemic Lesions Research Articles

Diagnostic imaging of Bacillus cereus brain infection in newborns.

Cerebral infection with the opportunistic pathogen Bacillus cereus can lead to severe lesions, especially in premature newborns. Early diagnosis would be highly beneficial. The aim of this study was to describe the imaging findings associated with B. cereus infections. We included all newborns with a positive B. cereus blood culture and transfontanellar ultrasound between 2012 and 2022 at the Tours University Hospital. Imaging was assessed by both a junior and a senior radiologist to differentiate between hemorrhages, leukomalacia, and lesions attributed to B. cereus. Nineteen patients were enrolled (12 girls), of whom 18 were premature. Three patients did not survive. Six patients had normal ultrasound and brain magnetic resonance imaging (MRI) scans. Thirteen patients had ultrasound-detected lesions: 7 hemorrhages, 1 case of leukomalacia, 1 focal ischemic lesion, and 5 lesions attributed to B. cereus. The B. cereus lesions appeared as irregular (5/5), bilateral (4/5), asymmetric (5/5), and hyperechoic patches in the subcortical white matter. They were extensive, asynchronous, and rapidly progressive over a few days (central necrosis with peripheral enhancement, referred to as the "bear scratch sign"), while respecting the cortex and basal ganglia. The presence of rapidly evolving white matter lesions should raise suspicion of B. cereus infection in newborns' brains. Imaging plays a crucial role in estimating the progression of this pathology.

The Motor Optimality Score-Revised Improves Early Detection of Unilateral Cerebral Palsy in Infants with Perinatal Cerebral Stroke.

Neonatal cerebral stroke includes a range of focal and multifocal ischemic and hemorrhagic brain lesions, occurring in about one of 3000 live births. More than 50% of children with neonatal stroke develop adverse outcomes, mainly unilateral cerebral palsy. Asymmetries in segmental movements at three months have been proven to be an early sign of CP in infants with unilateral brain damage. Recognition of additional early signs could enhance prognostic assessment and enable an early and targeted intervention. The aim of the study was to assess early signs of CP in infants with arterial cerebral stroke through the General Movements Assessment and the Motor Optimality Score-Revised (MOS-R). Twenty-four infants born at term (12 females and 12 males) diagnosed with ACS, and 24 healthy infants (16 females and 8 males) were assessed. The GMs (fidgety movements) and MOS-R were assessed from videos recorded at 11-14 weeks of post-term age. Cognitive and motor outcomes were assessed at 24 months using the Griffiths III developmental quotient and Amiel-Tison neurological examination. The gross motor function classification system expanded and revised (GMFCS-E&R) was adopted to categorize CP. Among infants with ACS, 21 (87.5%) developed unilateral CP. Most of them showed non-disabling CP (14 had GMFCS-E&R grade 1 [66.6%], 6 grade 2 [28.6%], and 1 grade 5 [4.8%]). Fidgety movements (FMs) were absent in 17 (70.8%), sporadic in 4 (16.7%) infants, and normal in 3 (12.5%). Segmental movement asymmetry was found in 22/24 (91.7%). According to the MOS-R, motor items (kicking, mouth movements), postural patterns (midline centered head, finger posture variability), and movement character (monotonous and stiff) were statistically different among infants with ACS and healthy infants. The MOS-R median global score was lower in the group with ACS compared to the control group (6 vs 26; p < 0.01). FMs, segmental movement asymmetry, and MOS-R global score were significantly correlated with abnormal outcome. MOS-R global scores less than or equal to 13 had 100% specificity and sensitivity in predicting GMFCS-E&R grade ≥ 2 CP in infants with ACS. The rate of CP was high among infants with ACS, but in most cases it showed low GMFCS-E&R grades. The study highlighted a significant correlation between MOS-R, together with absent FMs and unilateral CP in infants with ACS. Moreover, the MOS-R showed high sensitivity and specificity in the prediction of CP. Combined assessment of FMs and MOS-R could help to better identify infants at high risk of developing UCP in a population of infants with ACS. Early identification of precocious signs of unilateral CP is fundamental to providing an early individualized intervention.

Arterial Hypertension and Cognitive Disorders: What are the Risks?

Prevention of cognitive disorders and dementia is a major public health issue. Several studies have found a significant association between the existence of arterial hypertension and the onset of cognitive disorders and dementia (vascular or Alzheimer's disease) several years later. Arterial hypertension causes vascular changes that affect blood flow and brain metabolism. Cognitive disorders may be related to the presence of focal ischemic lesions (infarction, lacunae) and/or chronic white matter ischemia (leucoaraiosis) related to damage to the small cerebral arteries (arteriosclerosis). Recent work also suggests that cerebral hypoxia and endothelial function abnormalities lead to changes in the blood-brain barrier leading to an accumulation of β-amyloid protein in the brain and the formation of responsible amyloid plaques. of Alzheimer's disease. Few therapeutic trials have included cognitive assessment and/or diagnosis of dementia. They all raise some important criticisms: cognition is never the primary endpoint, follow-up is too short to study dementia; the evaluation of cognitive functions is very summary, the number of patients "lost to sight" is significant and the subjects at risk of developing dementia are in very low proportion.

A late-onset neurological disorder: Is progression inevitable? Expert Commentary

In this month's Movement Disorders Rounds, Dr. Shoaib Dal and colleagues describe an interesting patient with corticobasal syndrome (CBS) thought secondary to discrete asymmetric focal ischemic lesions affecting the cortical and immediate subcortical regions of the hand area of the primary motor cortex [1]. The patient was an 88 year-old right-handed man with a history of coronary artery disease who presented with recurrent presyncopal events and a 2-year history of slowly progressive left-hand clumsiness, tremor, and gait disturbance.

The impact of closed-loop intracortical stimulation on neural activity in brain-injured, anesthetized animals

BackgroundAcquired brain injuries, such as stroke, are a major cause of long-term disability worldwide. Intracortical microstimulation (ICMS) can be used successfully to assist in guiding appropriate connections to restore lost sensorimotor integration. Activity-Dependent Stimulation (ADS) is a specific type of closed-loop ICMS that aims at coupling the activity of two different brain regions by stimulating one in response to activity in the other. Recently, ADS was used to effectively promote behavioral recovery in rodent models following a unilateral traumatic brain injury in the primary motor cortex. While behavioral benefits have been described, the neurophysiological changes in spared areas in response to this type of stimulation have not been fully characterized. Here we explored how single-unit spiking activity is impacted by a focal ischemic lesion and, subsequently, by an ADS treatment.MethodsIntracortical microelectrode arrays were implanted in the ipsilesional rostral forelimb area (RFA) to record spike activity and to trigger intracortical microstimulation in the primary somatosensory area (S1) of anaesthetized Long Evans rats. An ischemic injury was induced in the caudal forelimb area through microinjections of Endothelin-1. Activity from both RFA and S1 was recorded and analyzed off-line by evaluating possible changes, either induced by the lesion in the Control group or by stimulation in the ADS group.ResultsWe found that the ischemic lesion in the motor area led to an overall increase in spike activity within RFA and a decrease in S1 with respect to the baseline condition. Subsequent treatment with ADS increased the firing rate in both RFA and S1. Post-stimulation spiking activity was significantly higher compared to pre-stimulation activity in the ADS animals versus non-stimulated controls. Moreover, stimulation promoted the generation of highly synchronized bursting patterns in both RFA and S1 only in the ADS group.ConclusionsThis study describes the impact on single-unit activity in ipsilesional areas immediately following a cortical infarct and demonstrates that application of ADS is effective in altering this activity.

LFP Analysis of Brain Injured Anesthetized Animals Undergoing Closed-Loop Intracortical Stimulation.

Activity dependent stimulation (ADS) is a closed loop stimulation technique whose neurophysiological effects have not been deeply investigated. Here we explored how Local field Potentials (LFP) are impacted by a focal ischemic lesion and, subsequently, by ADS treatment. Intracortical microelectrode arrays were implanted in the rostral forelimb area (RFA) and in the primary somatosensory area (S1) of anaesthetized rats. An ischemic injury was induced in the caudal forelimb area through microinjections of Endothelin-1. The lesion induced an acute depressive trend in LFP power in RFA (evaluated in 6 bands of interest: Delta (1–4Hz), Theta (4–8Hz), Alpha (8–11Hz), Beta (11–30Hz), LowGamma (30–55Hz) and HighGamma (55–80)) followed by a noticeable significant rebound in both areas. Applying ADS induced an overall decrease of power. The lesion impacted the connectivity in a frequency specific manner, resulting in widespread increase in connectivity in Delta both between and within areas. Two hours after the lesion, without stimulation, correlated activity between areas increased in Beta and Gamma. After stimulation, inter-area connectivity increased in Delta, Theta and Alpha, while considerably dropping within RFA in highGamma. By computing phase-amplitude coupling, we found that the lesion produced an incremental increase in the coupling between (Theta) Alpha phase and (lowGamma) highGamma amplitude within RFA, while S1 had a more generalized increase. Likewise, coupling between Theta phase and lowGamma/highGamma amplitudes increased between areas after lesion. ADS induced a similar increase, but greater in magnitude both within and between RFA and S1. These results have important implications on the emerging field of closed-loop adaptive stimulation promoting ADS as an innovative tool for the treatment of neurological disorders.

The chauffeur who banged cars happily: an interesting case of rapidly progressive strategic infarct dementia

AbstractBackgroundRapidly Progressive Dementias (RPDs) are a subtype of dementia which develop rapidly over few days to weeks or months and lead to varying neuro‐cognitive deficits. There are many causes of RPDs, like autoimmune, degenerative, metabolic, infectious, neoplastic and vascular. Majority of them are treatable if detected timely. We present an interesting case here.MethodA 41 year old male who worked as a chauffeur for a senior professor was brought to the Neurology department with a rather unusual complaint. The professor said that the chauffeur has been banging his car with other cars and road dividers while driving since 3 days. When enquired, he remained unapologetic about this. Also, he had been keeping mum during conversations. On taking history from wife, it was found that he had been forgetting simple things like names, keys, food and was staying aloof. Also, there had been bouts of over aggressiveness and violent behavior with very less sleep. Examination of the patient revealed fluctuating alertness, inattention and abulia with inability to perform any higher mental function test because of uncooperativeness. There was mild right hemiparesis too. Frontal lobe involvement was ascertained and imaging done.ResultMRI revealed few patchy areas of acute watershed infarcts in left frontal lobe, corona radiate, centrum semiovale and genu of corpus callosum (Figure 1). It was associated with left ICA thrombosis with significant narrowing. He was started on anti‐platelets and statins with mild improvement. He has been planned for carotid endarterectomy.ConclusionVascular infarcts are an important cause of RPDs. Infarcts in the genu of internal capsule are notorious for causing such presentations and hence also included in ‘Strategic Infarct Dementias’ (SIDs) which are characterized by focal ischemic lesions involving specific sites that are critical for higher cortical functions. Such cases require a careful history and examination along with relevant neuroimaging for proper diagnosis and treatment.

The Shh/Gli1 signaling pathway regulates regeneration via transcription factor Olig1 expression after focal cerebral ischemia in rats

ABSTRACT Objective Ischemic stroke is a major cause of death in the global population, with a high disability and mortality rate. Lack of regenerative ability is considered to be the fundamental cause. This study aims to determine the effect of Shh pathway, which mediates regenerative signaling in response to CNS injury, on myelin repair and Olig1 expression in focal ischemic lesions in the rat. Methods A model of middle cerebral artery occlusion (MCAO) was established using the intraluminal suture method where the middle cerebral artery (MCA) was restricted for 120 min. Cyclopamine, a specific inhibitor of Shh, or saline was administered 12h after MCAO surgery and lasted for 7d. After MCA occlusion, male Sprague-Dawley rats were randomly allocated to cyclopamine- or saline-treated groups. A group of no-injection animals after MCAO were used as control. The Shh signaling pathway, myelinogenesis-related factor MBP and Olig1 were tested using immunohistochemistry and RT-PCR assay. Results The levels of Shh and its component Gli1 were elevated from 1d up to 14d following ischemia, indicating that the Shh-Gli1 axis was broadly reactivated. Treatment with cyclopamine can partially block the Shh signaling pathway, prevent myelin repair, and decrease the Olig1 expression following ischemic stroke. Conclusion That blockade of Shh signaling concurrently with the creation of a lesion aggravated ischemic myelin damage, probably via its downstream effects on Olig1 transcription. Shh plays a contributory role during regeneration in the CNS, thereby providing promising new therapeutic strategies to assist in recovery from ischemic stroke.

Oral administration of cyclic glycyl-proline facilitates task learning in a rat stroke model

Cyclic glycyl-proline (cGP) exerts neuroprotective effects against ischemic stroke and may promote neural plasticity or network remodeling. We sought to determine to what extent oral administration of cGP could facilitate task learning in rats with ischemic lesions. We trained rats to perform a choice reaction time task using their forepaws. One week after changing the food to pellets containing cGP (no cGP: 0mg/kg; low cGP: 25mg/kg; and high cGP: 75mg/kg), we made a focal ischemic lesion on the left or right forepaw area of the sensorimotor cortex. After recovery of task performance, we altered the correct-response side of the task, and then analyzed the number of training days required for the rat to reach a learning criterion (error rate < 15%) and the regulation of adult neurogenesis in the subventricular zones (SVZs), taking lesion size into account. The low-cGP group required fewer training days for task learning than the no-cGP group. Unexpectedly, rats with larger lesions required fewer training days in the no-cGP and low-cGP groups, but more training days in the high-cGP group. The number of Ki67-immunopositive cells (indicating proliferative cells) in ipsilesional SVZ increased more rapidly in the low-cGP and high-cGP groups than in the no-cGP group. However, lesion size had only a small effect on required training days and the number of Ki67-immunopositive cells. We conclude that oral administration of cGP can facilitate task learning in rats with focal ischemic infarction through neural plasticity and network remodeling, even with minimal neuroprotective effects.

Secondary Degeneration of White Matter After Focal Sensorimotor Cortical Ischemic Stroke in Rats.

Ischemic lesions could lead to secondary degeneration in remote regions of the brain. However, the spatial distribution of secondary degeneration along with its role in functional deficits is not well understood. In this study, we explored the spatial and connectivity properties of white matter (WM) secondary degeneration in a focal unilateral sensorimotor cortical ischemia rat model, using advanced microstructure imaging on a 14 T MRI system. Significant axonal degeneration was observed in the ipsilateral external capsule and even remote regions including the contralesional external capsule and corpus callosum. Further fiber tractography analysis revealed that only fibers having direct axonal connections with the primary lesion exhibited a significant degeneration. These results suggest that focal ischemic lesions may induce remote WM degeneration, but limited to fibers tied to the primary lesion. These “direct” fibers mainly represent perilesional, interhemispheric, and subcortical axonal connections. At last, we found that primary lesion volume might be the determining factor of motor function deficits.

Covert strokes prior to Alzheimer’s disease onset accelerate peri-lesional pathology but not cognitive deficits in an inducible APP mouse model

It is estimated that up to 1 in 3 healthy middle-aged adults will have had a covert stroke during their lifetime. Furthermore, post-stroke, survivors are more than twice as likely to develop dementia. In the present study, we aimed to model the impact of focal subclinical ischemia prior to the onset of AD pathogenesis in a preclinical model. We utilized endothelin-1 to induce ischemia in an iducible transgenic mouse model of Alzheimer's disease, APPsi:tTA, allowing for temporal control of APP gene expression. We induced the focal subclinical ischemic events in the absence of APP expression, thus prior to AD onset. T2 structural magnetic resonance imaging confirmed the volume and location of focal subclinical ischemic lesions to the medial prefrontal cortex. Following recovery from surgery and 7weeks of APP expression, we found that two subclinical ischemic lesions resulted in a significant localized increase in amyloid load and in microglial activation proximal to the lesion. However, no differences were found in astrogliosis. A battery of behaviour tests was conducted, in which no significant differences were detected in activities of daily living and cognitive function between stroked and sham cohorts. Overall, our results demonstrated that APP expression was the sole driving force behind behavioural deficits. In conclusion, our results suggest that a history of two subclinical strokes prior to AD onset does not worsen early disease trajectory in a mouse model.

An integrative multivariate approach for predicting functional recovery using magnetic resonance imaging parameters in a translational pig ischemic stroke model.

Magnetic resonance imaging (MRI) is a clinically relevant, real-time imaging modality that is frequently utilized to assess stroke type and severity. However, specific MRI biomarkers that can be used to predict long-term functional recovery are still a critical need. Consequently, the present study sought to examine the prognostic value of commonly utilized MRI parameters to predict functional outcomes in a porcine model of ischemic stroke. Stroke was induced via permanent middle cerebral artery occlusion. At 24 hours post-stroke, MRI analysis revealed focal ischemic lesions, decreased diffusivity, hemispheric swelling, and white matter degradation. Functional deficits including behavioral abnormalities in open field and novel object exploration as well as spatiotemporal gait impairments were observed at 4 weeks post-stroke. Gaussian graphical models identified specific MRI outputs and functional recovery variables, including white matter integrity and gait performance, that exhibited strong conditional dependencies. Canonical correlation analysis revealed a prognostic relationship between lesion volume and white matter integrity and novel object exploration and gait performance. Consequently, these analyses may also have the potential of predicting patient recovery at chronic time points as pigs and humans share many anatomical similarities (e.g., white matter composition) that have proven to be critical in ischemic stroke pathophysiology. The study was approved by the University of Georgia (UGA) Institutional Animal Care and Use Committee (IACUC; Protocol Number: A2014-07-021-Y3-A11 and 2018-01-029-Y1-A5) on November 22, 2017.

Neuronal protein-tyrosine phosphatase 1B hinders sensory-motor functional recovery and causes affective disorders in two different focal ischemic stroke models.

Ischemic brain injury causes neuronal death and inflammation. Inflammation activates protein-tyrosine phosphatase 1B (PTP1B). Here, we tested the significance of PTP1B activation in glutamatergic projection neurons on functional recovery in two models of stroke: by photothrombosis, focal ischemic lesions were induced in the sensorimotor cortex (SM stroke) or in the peri-prefrontal cortex (peri-PFC stroke). Elevated PTP1B expression was detected at 4 days and up to 6 weeks after stroke. While ablation of PTP1B in neurons of neuronal knockout (NKO) mice had no effect on the volume or resorption of ischemic lesions, markedly different effects on functional recovery were observed. SM stroke caused severe sensory and motor deficits (adhesive removal test) in wild type and NKO mice at 4 days, but NKO mice showed drastically improved sensory and motor functional recovery at 8 days. In addition, peri-PFC stroke caused anxiety-like behaviors (elevated plus maze and open field tests), and depression-like behaviors (forced swimming and tail suspension tests) in wild type mice 9 and 28 days after stroke, respectively, with minimal effect on sensory and motor function. Peri-PFC stroke-induced affective disorders were associated with fewer active (FosB+) neurons in the PFC and nucleus accumbens but more FosB+ neurons in the basolateral amygdala, compared to sham-operated mice. In contrast, mice with neuronal ablation of PTP1B were protected from anxiety-like and depression-like behaviors and showed no change in FosB+ neurons after peri-PFC stroke. Taken together, our study identifies neuronal PTP1B as a key component that hinders sensory and motor functional recovery and also contributes to the development of anxiety-like and depression-like behaviors after stroke. Thus, PTP1B may represent a novel therapeutic target to improve stroke recovery. All procedures for animal use were approved by the Animal Care and Use Committee of the University of Ottawa Animal Care and Veterinary Service (protocol 1806) on July 27, 2018.

A Neurological Appearance of Celiac Disease: Is There Any Associated Factor?

Celiac disease may present with one or more neurological signs and/or symptoms. We aimed to define the incidence of accompanying neurological manifestations in children diagnosed as having celiac disease. The prospective study included 146 children diagnosed as having celiac disease. The medical records (presentation symptoms, clinical findings, serological test, duodenal biopsy results, lack/deficiency of vitamin, tissue type, accompanying autoimmune disorders) and demographic data of all patients were also reviewed. Thirty-five (23.9%) of the 146 celiac patients exhibited one or more neurological findings. Headache (11.6%) and dizziness (6.1%) were the most common symptoms among neurological manifestations. There was a significant difference between the patients with and without neurological manifestations in terms of sex, biopsy result, and tissue type (P < 0.05). Moreover, there was a statistically significant difference between tissue types of the patients with and without headache (P < 0.05). We found that grade 3a by Marsh classification was the most common type among the patients with and without neurological findings in celiac disease. On neuroimaging evaluation of patients, 1 patient with chronic focal ischemic lesion, 1 patient with Chiari type 1 malformation, and 1 patient with subcortical white matter changes were identified. Pathophysiology of neurological involvement in celiac disease is liable for various neurological findings. This study contributes to data suggesting that female sex, mild histopathological form, and human leukocyte antigen DQ2 heterozygosity are related to neurological manifestations, and also human leukocyte antigen DQ2 heterozygosity is associated with headache in celiac disease.

Restrictive Cardiomyopathy Revealing Systemic Sclerodermia

Primary myocardial involvement is common in systemic sclerosis. There is growing evidence strongly suggesting that this involvement is linked to repeated focal ischemic lesions causing irreversible myocardial fibrosis. It can affect all heart structures. We report the case of a 65 years old male patient, without any personal medical history, admitted for inaugural right heart decompensation. The diagnosis of restrictive cardiomyopathy is based mainly on the following criteria: on echocardiography, hypertrohy of the right ventricle with alteration of the longitudinal systolic function, dilation of the right atrium, with good overall contractility. On right cardiac catheterization: elevation and equalization of the telesystolic pressures of the right atrium, right ventricle, and pulmonary artery with appearance of dip plateau on the right ventricle curve. Scleroderma was evoked considering following statements: the presence of Raynaud's phenomenon, unknown by the patient (presence of dermal sclerosis with pericapillary oedema and capillary dystrophy on capillaroscopy), cutaneous involvement (presence of perivascular and perineural mononuclear infiltrates, with collagen fibers increased in number and thickness), pulmonary involvement (diffuse bilateral interstitial lung disease) and renal involvement (moderately impaired function and positive proteinuria). The concept of cardiac dysfunction in scleroderma and other rheumatologic conditions has received new interest with the advent of newer non-invasive imaging techniques. Therfore, it would be necessary to search the cardiac involvement especially subclinical one in this type of system disease, as well as to confirm the systemic origin in front of certain forms of cardiopathies in particular restrictive cardiomyopathy.

Restrictive Cardiomyopathy Revealing Systemic Sclerodermia

Primary myocardial involvement is common in systemic sclerosis. There is growing evidence strongly suggesting that this involvement is linked to repeated focal ischemic lesions causing irreversible myocardial fibrosis. It can affect all heart structures. We report the case of a 65 years old male patient, without any personal medical history, admitted for inaugural right heart decompensation. The diagnosis of restrictive cardiomyopathy is based mainly on the following criteria: on echocardiography, hypertrohy of the right ventricle with alteration of the longitudinal systolic function, dilation of the right atrium, with good overall contractility. On right cardiac catheterization: elevation and equalization of the telesystolic pressures of the right atrium, right ventricle, and pulmonary artery with appearance of dip plateau on the right ventricle curve. Scleroderma was evoked considering following statements: the presence of Raynaud's phenomenon, unknown by the patient (presence of dermal sclerosis with pericapillary oedema and capillary dystrophy on capillaroscopy), cutaneous involvement (presence of perivascular and perineural mononuclear infiltrates, with collagen fibers increased in number and thickness), pulmonary involvement (diffuse bilateral interstitial lung disease) and renal involvement (moderately impaired function and positive proteinuria). The concept of cardiac dysfunction in scleroderma and other rheumatologic conditions has received new interest with the advent of newer non-invasive imaging techniques. Therfore, it would be necessary to search the cardiac involvement especially subclinical one in this type of system disease, as well as to confirm the systemic origin in front of certain forms of cardiopathies in particular restrictive cardiomyopathy.

Recovery of contralesional saccade choice and reaction time deficits after a unilateral endothelin-1-induced lesion in the macaque caudal prefrontal cortex.

The caudal primate prefrontal cortex (PFC) is involved in target selection and visually guided saccades through both covert attention and overt orienting eye movements. Unilateral damage to the caudal PFC often leads to decreased awareness of a contralesional target alone, referred to as "neglect," or when it is presented simultaneously with an ipsilesional target, referred to as "extinction." In the current study, we examined whether deficits in contralesional target selection were due to contralesional oculomotor deficits, such as slower reaction times. We experimentally induced a focal ischemic lesion in the right caudal PFC of 4 male macaque monkeys using the vasoconstrictor endothelin-1 and measured saccade choice and reaction times on double-stimulus free-choice tasks and single-stimulus trials before and after the lesion. We found that 1) endothelin-1-induced lesions in the caudal PFC produced contralesional target selection deficits that varied in severity and duration based on lesion volume and location; 2) contralesional neglect-like deficits were transient and recovered by week 4 postlesion; 3) contralesional extinction-like deficits were longer lasting and recovered by weeks 8-16 postlesion; 4) contralesional reaction time returned to baseline well before the contralesional choice deficit had recovered; and 5) neither the mean reaction times nor the reaction time distributions could account for the degree of contralesional extinction on the free-choice task throughout recovery. These findings demonstrate that the saccade choice bias observed after a right caudal PFC lesion is not exclusively due to contralesional motor deficits, but instead reflects a combination of impaired motor and attentional processing.NEW & NOTEWORTHY Unilateral damage to the caudal prefrontal cortex in macaque monkeys results in impaired contralesional target selection during the simultaneous presentation of an ipsilesional target. We show that the recovery of contralesional target selection cannot be explained by the recovery of prolonged contralesional saccadic reaction times alone. This indicates that an impairment in contralesional attentional processing contributes to the magnitude of the saccade choice bias in the weeks following a unilateral caudal prefrontal cortex lesion.

Complement component 1q subcomponent binding protein in the brain of the rat

Complement component 1q subcomponent binding protein (C1qbp) is a multifunctional protein involved in immune response, energy homeostasis of cells as a plasma membrane receptor, and a nuclear, cytoplasmic or mitochondrial protein. Recent reports suggested its neuronal function, too, possibly in axon maintenance, synaptic function, and neuroplasticity. Therefore, we addressed to identify C1qbp in the rat brain using in situ hybridization histochemistry and immunolabelling at light and electron microscopic level. C1qbp has a topographical distribution in the brain established by the same pattern of C1qbp mRNA-expressing and protein-containing neurons with the highest abundance in the cerebral cortex, anterodorsal thalamic nucleus, hypothalamic paraventricular (PVN) and arcuate nuclei, spinal trigeminal nucleus. Double labelling of C1qbp with the neuronal marker NeuN, with the astrocyte marker S100, and the microglia marker Iba1 demonstrated the presence of C1qbp in neurons but not in glial cells in the normal brain, while C1qbp appeared in microglia following their activation induced by focal ischemic lesion. Only restricted neurons expressed C1qbp, for example, in the PVN, magnocellular neurons selectively contained C1qbp. Further double labelling by using the mitochondria marker Idh3a antibody suggested the mitochondrial localization of C1qbp in the brain, confirmed by correlated light and electron microscopy at 3 different brain regions. Post-embedding immunoelectron microscopy also suggested uneven C1qbp content of mitochondria in different brain areas but also heterogeneity within single neurons. These data suggest a specific function of C1qbp in the brain related to mitochondria, such as the regulation of local energy supply in neuronal cells.

Spontaneous astrocytic Ca2+ activity abounds in electrically suppressed ischemic penumbra of aged mice.

Experimental focal cortical ischemic lesions consist of an ischemic core and a potentially salvageable peri-ischemic region, the ischemic penumbra. The activity of neurons and astrocytes is assumed to be suppressed in the penumbra because the electrical function is interrupted, but this is incompletely elucidated. Most experimental stroke studies used young adult animals, whereas stroke is prevalent in the elderly population. Using two-photon imaging in vivo, we here demonstrate extensive but electrically silent, spontaneous Ca2+ activity in neurons and astrocytes in the ischemic penumbra of 18- to 24-month-old mice 2-4 hr after middle cerebral artery occlusion. In comparison, stroke reduced spontaneous Ca2+ activity in neurons and astrocytes in adult mice (3-4 months of age). In aged mice, stroke increased astrocytic spontaneous Ca2+ activity considerably while neuronal spontaneous Ca2+ activity was unchanged. Blockade of action potentials and of purinergic receptors strongly reduced spontaneous Ca2+ activity in both neurons and astrocytes in the penumbra of old stroke mice. This indicates that stroke had a direct influence on mechanisms in presynaptic terminals and on purinergic signaling. Thus, highly dynamic variations in spontaneous Ca2+ activity characterize the electrically compromised penumbra, with remarkable differences between adult and old mice. The data are consistent with the notion that aged neurons and astrocytes take on a different phenotype than young mice. The increased activity of the aged astrocyte phenotype may be harmful to neurons. We suggest that the abundant spontaneous Ca2+ activity in astrocytes in the ischemic penumbra of old mice may be a novel target for neuroprotection strategies. A video abstract of this article can be found at https://youtu.be/AKlwKFsz1qE.

Evaluation of temperature induction in focal ischemic thermocoagulation model.

The thermocoagulation model, which consists of focal cerebral ischemia with craniectomy, is helpful in studying permanent ischemic brain lesions and has good reproducibility and low mortality. This study analyzed the best conditions for inducing a focal ischemic lesion by thermocoagulation. We investigated parameters such as temperature and thermal dissipation in the brain tissue during induction and analyzed real-time blood perfusion, histological changes, magnetic resonance imaging (MRI), and motor behavior in a permanent ischemic stroke model. We used three-month-old male Wistar rats, weighing 300–350 g. In the first experiment, the animals were divided into four groups (n = 5 each): one sham surgery group and three ischemic lesion groups having thermocoagulation induction (TCI) temperatures of 200°C, 300°C, and 400°C, respectively, with blood perfusion (basal and 30 min after TCI) and 2,3,5-Triphenyl-tetrazolium chloride (TTC) evaluation at 2 h after TCI. In the second experiment, five groups (n = 5 each) were analyzed by MRI (basal and 24 h after TCI) and behavioral tests (basal and seven days after TCI) with the control group added for the surgical effects. The MRI and TTC analyses revealed that ischemic brain lesions expressively evolved, especially at TCI temperatures of 300°C and 400°C, and significant motor deficits were observed as the animals showed a decrease frequency of movement and an asymmetric pattern. We conclude that a TCI temperature of 400°C causes permanent ischemic stroke and motor deficit.