Cerebral Microhemorrhages Research Articles

Plasma proteome-wide analysis of cerebral small vessel disease identifies novel biomarkers and disease pathways.

Cerebral small vessel disease (SVD), as defined by neuroimaging characteristics such as white matter hyperintensities (WMHs), cerebral microhemorrhages (CMHs), and lacunar infarcts, is highly prevalent and has been associated with dementia risk and other clinical sequelae. Although conditions such as hypertension are known to contribute to SVD, little is known about the diverse set of subclinical biological processes and molecular mediators that may also influence the development and progression of SVD. To better understand the mechanisms underlying SVD and to identify novel SVD biomarkers, we used a large-scale proteomic platform to relate 4,877 plasma proteins to MRI-defined SVD characteristics within 1,508 participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort. Our proteome-wide analysis of older adults (mean age: 76) identified 13 WMH-associated plasma proteins involved in synaptic function, endothelial integrity, and angiogenesis, two of which remained associated with late-life WMH volume when measured nearly 20 years earlier, during midlife. We replicated the relationship between 9 candidate proteins and WMH volume in one or more external cohorts; we found that 11 of the 13 proteins were associated with risk for future dementia; and we leveraged publicly available proteomic data from brain tissue to demonstrate that a subset of WMH-associated proteins was differentially expressed in the context of cerebral atherosclerosis, pathologically-defined Alzheimer's disease, and cognitive decline. Bidirectional two-sample Mendelian randomization analyses examined the causal relationships between candidate proteins and WMH volume, while pathway and network analyses identified discrete biological processes (lipid/cholesterol metabolism, NF-kB signaling, hemostasis) associated with distinct forms of SVD. Finally, we synthesized these findings to identify two plasma proteins, oligodendrocyte myelin glycoprotein (OMG) and neuronal pentraxin receptor (NPTXR), as top candidate biomarkers for elevated WMH volume and its clinical manifestations.

The vasoprotective role of IGF-1 signaling in the cerebral microcirculation: prevention of cerebral microhemorrhages in aging.

Aging is closely associated with various cerebrovascular pathologies that significantly impact brain function, with cerebral small vessel disease (CSVD) being a major contributor to cognitive decline in the elderly. Consequences of CSVD include cerebral microhemorrhages (CMH), which are small intracerebral bleeds resulting from the rupture of microvessels. CMHs are prevalent in aging populations, affecting approximately 50% of individuals over 80, and are linked to increased risks of vascular cognitive impairment and dementia (VCID). Hypertension is a primary risk factor for CMHs. Vascular smooth muscle cells (VSMCs) adapt to hypertension by undergoing hypertrophy and producing extracellular matrix (ECM) components, which reinforce vessel walls. Myogenic autoregulation, which involves pressure-induced constriction, helps prevent excessive pressure from damaging the vulnerable microvasculature. However, aging impairs these adaptive mechanisms, weakening vessel walls and increasing susceptibility to damage. Insulin-like Growth Factor 1 (IGF-1) is crucial for vascular health, promoting VSMC hypertrophy, ECM production, and maintaining normal myogenic protection. IGF-1 also prevents microvascular senescence, reduces reactive oxygen species (ROS) production, and regulates matrix metalloproteinase (MMP) activity, which is vital for ECM remodeling and stabilization. IGF-1 deficiency, common in aging, compromises these protective mechanisms, increasing the risk of CMHs. This review explores the vasoprotective role of IGF-1 signaling in the cerebral microcirculation and its implications for preventing hypertension-induced CMHs in aging. Understanding and addressing the decline in IGF-1 signaling with age are crucial for maintaining cerebrovascular health and preventing hypertension-related vascular injuries in the aging population.

Research on the precise recognition stage of cerebral microhemorrhage based on deep learning algorithm

Cerebral microbleeds (CMB) is an important type of cerebral microbleeds. In recent years, many studies have proved that CMB can not only cause vascular dementia, but also increase the risk of stroke. Therefore, detection of CMB is of great clinical significance for balancing antithrombotic therapy and risk assessment in stroke patients, and detection of CMB is of great value for diagnosis and prognosis of cranial injury. This paper mainly proposes a two-stage CMB detection framework based on deep learning, which includes the screening stage of brain microhemorrhagic candidate points and the recognition stage of brain microhemorrhagic points based on deep learning. Firstly, in the first stage, we screened CMB candidate points by combining rapid radial transformation and threshold segmentation, and excluded a large number of background regions and obvious non-CMB regions. Then, in the second stage, the two-channel images spliced by sensitivity weighted imaging (SWI) and phase diagram (Pha) were used for false positive judgment by 3D convolutional neural network to distinguish the true CMB from the CMB analog.

The impact of cerebral microhemorrhage on antithrombotic strategies in patients with cardiovascular and cerebrovascular diseases

The impact of cerebral microhemorrhage on antithrombotic strategies in patients with cardiovascular and cerebrovascular diseases

A quantitative MRI comparative study of imaging markers for cerebral small vessel disease in the middle-aged and elderly patients with and without hypertension

Objective: To explore the difference of MRI markers of small cerebral vascular disease in middle-aged and elderly patients with hypertension and non-hypertension. Methods: A cross-sectional study. The clinical data of 316 patients who underwent head MRI with susceptibility weighted imaging scans at the Affiliated Zhongda Hospital of Southeast University from November 2013 to August 2022 were retrospectively analyzed, including 190 males and 126 females, with the age of (71.6±8.9)years. According to the history of hypertension, the patients were divided into hypertension group(n=259) and the non-hypertension group(n=57). The patients in the non-hypertension group were further divided into abnormal blood pressure group on admission (n=19) and normal blood pressure group on admission (n=38). The imaging features of different CSVD dimensions in the patient's images were quantified or graded and compared between hypertensive and non-hypertensive patient groups. Deep learning methods were employed to segment white matter lesions, and voxel-wise analysis was conducted to investigate the differences in whole-brain white matter lesion probability between patients in both groups. Spearman correlation analysis was used to analyze the correlation between hypertension and small cerebral vascular disease. Results: Compared with the non-hypertensive group, the cerebral microhemorrhage count, deep microhemorrhage count, basal ganglia level lacunae count, perivascular space (EPVS) grade of hemioval center level and EPVS grade of basal ganglia level were higher in the hypertensive group (all P<0.05). The cerebral microhemorrhage count [3.0(1.0, 15.0) vs 1.0 (0, 4.2)], deep microhemorrhage count [1.0 (0, 7.0) vs 1.0 (0, 4.2)] and EPVS classification at basal ganglium level [2.0(1.0, 3.0) vs 1.0(1.0, 2.0)] in the group with history of hypertension were higher than those in the group with normal blood pressure at admission (all P<0.05). The EPVS grade at the central level of the semiovale in the hypertension group was higher than that of the group with normal blood pressure at admission [2.0(1.0, 2.0) vs 1.0 (1.0, 2.0)], and also higher than that of the group with abnormal blood pressure at admission [2.0(1.0, 2.0) vs 1.0(1.0, 2.0)](both P<0.05). Voxel-by-voxel analysis showed no significant difference in the probability of white matter lesions in the whole brain between patients with and without a history of hypertension, but patients with a history of hypertension showed more extensive para-ventricular white matter hypersignaling than those without a history of hypertension. Spearman correlation analysis showed that hypertension grade was correlated with the number of microbleeding lesions in depth (r=0.149), the number of lacunae lesions in the center of the hemioval (r=0.209), and the number of lacunae lesions in the basal ganglia (r=0.204) (all P<0.05). Conclusions: Chronic hypertension can affect different dimensions of small vessel disease imaging, primarily manifested in the increases of deep microbleed counts and the EPVS grade.

Longitudinal detection of gait alterations associated with hypertension-induced cerebral microhemorrhages in mice: predictive role of stride length and stride time asymmetry and increased gait entropy

Cerebral microhemorrhages (CMHs) are of paramount importance as they not only signify underlying vascular pathology but also have profound implications for cognitive function and neurological health, serving as a critical indicator for the early detection and management of vascular cognitive impairment (VCI). This study aimed to investigate the effects of hypertension-induced CMHs on gait dynamics in a mouse model, focusing on the utility of advanced gait metrics as sensitive indicators of subclinical neurological alterations associated with CMHs. To induce CMHs, we employed a hypertensive mouse model, using a combination of Angiotensin II and L-NAME to elevate blood pressure, further supplemented with phenylephrine to mimic transient blood pressure fluctuations. Gait dynamics were analyzed using the CatWalk system, with emphasis on symmetry indices for Stride Length (SL), Stride Time (ST), and paw print area, as well as measures of gait entropy and regularity. The study spanned a 30-day experimental period, capturing day-to-day variations in gait parameters to assess the impact of CMHs. Temporary surges in gait asymmetry, detected as deviations from median gait metrics, suggested the occurrence of subclinical neurological signs associated with approximately 50% of all histologically verified CMHs. Our findings also demonstrated that increases in gait entropy correlated with periods of increased gait asymmetry, providing insights into the complexity of gait dynamics in response to CMHs. Significant correlations were found between SL and ST symmetry indices and between these indices and the paw print area symmetry index post-hypertension induction, indicating the interdependence of spatial and temporal aspects of gait affected by CMHs. Collectively, advanced gait metrics revealed sensitive, dynamic alterations in gait regulation associated with CMHs, resembling the temporal characteristics of transient ischemic attacks (TIAs). This underscores their potential as non-invasive indicators of subclinical neurological impacts. This study supports the use of detailed gait analysis as a valuable tool for detecting subtle neurological changes, with implications for the early diagnosis and monitoring of cerebral small vessel disease (CSVD) in clinical settings.

Temporal Characterization of the Amyloidogenic APPswe/PS1dE9;hAPOE4 Mouse Model of Alzheimer's Disease.

Alzheimer's disease (AD) is a devastating disorder with a global prevalence estimated at 55 million people. In clinical studies administering certain anti-beta-amyloid (Aβ) antibodies, amyloid-related imaging abnormalities (ARIAs) have emerged as major adverse events. The frequency of these events is higher among apolipoprotein ε4 allele carriers (APOE4) compared to non-carriers. To reflect patients most at risk for vascular complications of anti-Aβ immunotherapy, we selected an APPswe/PS1dE9 transgenic mouse model bearing the human APOE4 gene (APPPS1:E4) and compared it with the same APP/PS1 mouse model bearing the human APOE3 gene (APOE ε3 allele; APPPS1:E3). Using histological and biochemical analyses, we characterized mice at three ages: 8, 12, and 16 months. Female and male mice were assayed for general cerebral fibrillar and pyroglutamate (pGlu-3) Aβ deposition, cerebral amyloid angiopathy (CAA), microhemorrhages, apoE and cholesterol composition, astrocytes, microglia, inflammation, lysosomal dysfunction, and neuritic dystrophy. Amyloidosis, lipid deposition, and astrogliosis increased with age in APPPS1:E4 mice, while inflammation did not reveal significant changes with age. In general, APOE4 carriers showed elevated Aβ, apoE, reactive astrocytes, pro-inflammatory cytokines, microglial response, and neuritic dystrophy compared to APOE3 carriers at different ages. These results highlight the potential of the APPPS1:E4 mouse model as a valuable tool in investigating the vascular side effects associated with anti-amyloid immunotherapy.

Angiogenesis and Microvascular Permeability.

Angiogenesis, the formation of new blood microvessels, is a necessary physiological process for tissue generation and repair. Sufficient blood supply to the tissue is dependent on microvascular density, while the material exchange between the circulating blood and the surrounding tissue is controlled by microvascular permeability. We thus begin this article by reviewing the key signaling factors, particularly vascular endothelial growth factor (VEGF), which regulates both angiogenesis and microvascular permeability. We then review the role of angiogenesis in tissue growth (bone regeneration) and wound healing. Finally, we review angiogenesis as a pathological process in tumorigenesis, intraplaque hemorrhage, cerebral microhemorrhage, pulmonary fibrosis, and hepatic fibrosis. Since the glycocalyx is important for both angiogenesis and microvascular permeability, we highlight the role of the glycocalyx in regulating the interaction between tumor cells and endothelial cells (ECs) and VEGF-containing exosome release and uptake by tumor-associated ECs, all of which contribute to tumorigenesis and metastasis.

Cortical Microhemorrhage Presentation of Small Vessel Primary Angiitis of the Central Nervous System.

Primary angiitis of the central nervous system (PACNS) is a rare vasculitis restricted to the brain, spinal cord, and leptomeninges. This study aimed to describe the imaging characteristics of patients with small vessel PACNS (SV-PACNS) using 7 T magnetic resonance imaging (MRI). This ongoing prospective observational cohort study included patients who met the Calabrese and Mallek criteria and underwent 7 T MRI scan. The MRI protocol includes T1-weighted magnetization-prepared rapid gradient echo imaging, T2 star weighted imaging, and susceptibility-weighted imaging. Two experienced readers independently reviewed the neuroimages. Clinical data were extracted from the electronic patient records. The findings were then applied to a cohort of patients with large vessel central nervous system (CNS) vasculitis. We included 21 patients with SV-PACNS from December 2021 to November 2023. Of these, 12 (57.14%) had cerebral cortical microhemorrhages with atrophy. The pattern with microhemorrhages was described in detail based on the gradient echo sequence, leading to the identification of what we have termed the "coral-like sign." The onset age of patients with coral-like sign (33.83 ± 9.93 years) appeared younger than that of patients without coral-like sign (42.11 ± 14.18 years) (P = 0.131). Furthermore, the cerebral lesions in patients with cortical microhemorrhagic SV-PACNS showed greater propensity toward bilateral lesions (P = 0.03). The coral-like sign was not observed in patients with large vessel CNS vasculitis. The key characteristics of the coral-like sign represent cerebral cortical diffuse microhemorrhages with atrophy, which may be an important MRI pattern of SV-PACNS. ANN NEUROL 2024;96:194-203.

Diffuse cerebral microhemorrhages in Wiskott-Aldrich syndrome – A rare radiological manifestation of a rare immunodeficiency disorder

Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency disorder with the characteristic triad of immunodeficiency, thrombocytopenia, and eczema. It results from a genetic mutation in the gene encoding WAS protein. We present a case of a 4-year-old male child who presented with two episodes of generalised tonic clonic seizures (GTCS) type convulsions. Magnetic resonance imaging (MRI) brain with contrast revealed diffuse cerebral microhemorrhages in supratentorial and infratentorial brain parenchyma which is a rare manifestation and not adequately documented in literature to the best of our knowledge.

Lecanemab: A Second in Class Therapy for the Management of Early Alzheimer's Disease.

The Food and Drug Administration granted traditional approval of lecanemab for the treatment of Alzheimer's disease (AD). Lecanemab is a humanized anti-amyloid monoclonal antibody directed towards Aβ protofibrils. Lecanemab is the only drug that targets Aβ soluble protofibrils and has shown statistical differences in mild AD or mild cognitive impairment. In its landmark phase III trial, lecanemab was shown to slow the progression of clinical decline, and a reduction in amyloid protein accumulation. The difference in mean CDR-SOB score improvement between the treatment and placebo groups was -0.45, of which the clinical significance could be argued. Amyloid burden was also considerably reduced as well, but the true clinical consequence of this reduction remains to be seen. This beneficial impact on daily living is offset by rare but serious side effects including amyloid-related imaging abnormalities (ARIA) causing cerebral edema (ARIA-E) or cerebral microhemorrhages or hemosiderin deposits (ARIA-H). Benefits of therapy must be considered against the risk of cerebral microhemorrhages and edema. Affordability must also be taken into consideration. The current estimated yearly cost for twice monthly lecanemab infusion is $26,500. In addition to the significant cost challenges, the frequent infusions may pose concerns related to access. Additional agents within this class are in the pipelines with possibly increased efficacy or decreased adverse events.

Cerebral microbleeds: Causes, clinical relevance, and imaging approach - A narrative review.

With advances in magnetic resonance imaging (MRI) sequences, there has been increased identification of microbleed/microhemorrhage across different population ages, but more commonly in the older age group. These are defined as focal areas of signal loss on gradient echo MRI sequences (T2* and susceptibility-weighted images), which are usually <5 mm in size representing hemosiderin deposition with wide ranges of etiologies. Susceptibility-weighted imaging (SWI) has become a routine MRI sequence for practices across the globe resulting in better identification of these entities. Over the past decade, there has been a better understanding of the clinical significance of microbleeds including their prognostic value in ischemic and hemorrhagic stroke. Cerebral amyloid angiopathy and hypertension are the two most common causes of microbleeds following peripheral and central pattern, respectively. In the younger age group, microbleeds are more common due to familial conditions or a wide range of hypercoagulable states. This review outlines the pathophysiology, prevalence, and clinical implications of cerebral microhemorrhage along with a brief discussion about the technical considerations of SWI.

Comparative Efficacy and Safety of Monoclonal Antibodies for Cognitive Decline in Patients with Alzheimer's Disease: A Systematic Review and Network Meta-Analysis.

Recent clinical trials of anti-Aβ monoclonal antibodies (mAbs) in the treatment of early Alzheimer's disease (AD) have produced encouraging cognitive and clinical results. The purpose of this network meta-analysis (NMA) was to compare and rank mAb drugs according to their efficacy and safety. PubMed, Embase, Web of Science, and the Cochrane Library were searched for randomized controlled trials testing various mAbs for the treatment of cognitive decline in patients with AD, up to March 31, 2023. R software (version 4.2.3) along with JAGS and STATA software (version 15.0) were used for statistical analysis. Odds ratio (OR) for binary variables, mean difference (MD) for continuous variables, and their 95% confidence intervals (CI) were utilized to estimate treatment effects and rank probabilities for each mAb in terms of safety and efficacy outcomes. We calculated the surface under the cumulative ranking area (SUCRA) to evaluate each mAb, with higher SUCRA values indicating better efficacy or lower likelihood of adverse events. Thirty-three randomized controlled trials with a total of 21,087 patients were included in the current NMA, involving eight different mAbs. SUCRA values showed that aducanumab (87.01% and 99.37%, respectively) was the most likely to achieve the best therapeutic effect based on the changes of Mini-Mental State Examination (MMSE) and Clinical Dementia Rating scale Sum of Boxes (CDR-SB) scores. Donanemab (88.50% and 99.00%, respectively) performed better than other therapies for Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and Positron Emission Tomography-Standardized Uptake Value ratio (PET-SUVr). Lecanemab (87.24%) may be the most promising way to slow down the decrease of Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) score. In the analysis of the incidence of adverse events (subjects with any treatment-emergent adverse event), gantenerumab (89.12%) had the least potential for adverse events, while lecanemab (0.79%) may cause more adverse events. Solanezumab (95.75% and 80.38%, respectively) had the lowest incidence of amyloid-related imaging abnormalities characterized by edema and effusion (ARIA-E) and by cerebral microhemorrhages (ARIA-H) of the included immunotherapies. While SUCRA values provided a comprehensive measure of treatment efficacy, the inherent statistical uncertainty required careful analysis in clinical application. Despite immunotherapies significantly increasing the risks of adverse events and ARIA, the data suggest that mAbs can effectively improve the cognitive function of patients with mild and moderate AD. According to the NMA, aducanumab was the most likely to achieve significant improvements in different cognitive and clinical assessments (statistically improved MMSE and CDR-SB), followed by donanemab (statistically improved ADAS-Cog, and PET-SUVr) and lecanemab (statistically improved ADCS-ADL).

Vascular smooth muscle cell-specific Igf1r deficiency exacerbates the development of hypertension-induced cerebral microhemorrhages and gait defects.

Cerebrovascular fragility and cerebral microhemorrhages (CMH) contribute to age-related cognitive impairment, mobility defects, and vascular cognitive impairment and dementia, impairing healthspan and reducing quality of life in the elderly. Insulin-like growth factor 1 (IGF-1) is a key vasoprotective growth factor that is reduced during aging. Circulating IGF-1 deficiency leads to the development of CMH and other signs of cerebrovascular dysfunction. Here our goal was to understand the contribution of IGF-1 signaling on vascular smooth muscle cells (VSMCs) to the development of CMH and associated gait defects. We used an inducible VSMC-specific promoter and an IGF-1 receptor (Igf1r) floxed mouse line (Myh11-CreERT2 Igf1rf/f) to knockdown Igf1r. Angiotensin II in combination with L-NAME-induced hypertension was used to elicit CMH. We observed that VSMC-specific Igf1r knockdown mice had accelerated development of CMH, and subsequent associated gait irregularities. These phenotypes were accompanied by upregulation of a cluster of pro-inflammatory genes associated with VSMC maladaptation. Collectively our findings support an essential role for VSMCs as a target for the vasoprotective effects of IGF-1, and suggest that VSMC dysfunction in aging may contribute to the development of CMH.

Risk factors in developing amyloid related imaging abnormalities (ARIA) and clinical implications.

Alzheimer's disease (AD) affects over 6 million people over the age of 65. The advent of new anti-amyloid monoclonal antibodies as treatment for early Alzheimer's disease these immunotherapeutics may slow disease progression but also pose significant risks. Amyloid related imaging abnormalities (ARIA) identified on MRI following administration of these new monoclonal antibodies can cause both brain edema (ARIA-E) and hemorrhage (ARIA-H). While most ARIA is asymptomatic, some patients can develop headache, confusion, nausea, dizziness, seizures and in rare cases death. By analyzing lecanemab, aducanumab, gantenerumab, donanemab, and bapineuzumab clinical trials; risk factors for developing ARIA can be identified to mitigate some of the ARIA risk. Risk factors for developing ARIA-E are a positive Apoε4 carrier status and prior multiple cerebral microhemorrhages. Risk factors for ARIA-H are age, antithrombotic use, and history of prior strokes. With lecanemab, ARIA-E and ARIA-H were seen at lower rates 12 and 17%, respectively, compared to aducanumab (ARIA-E 35% and ARIA-H 19%) in treated patients. ARIA risk factors have impacted inclusion and exclusion criteria, determining who can receive lecanemab. In some clinics, almost 90% of Alzheimer's patients are excluded from receiving these new anti-amyloid therapeutics. This review aims to discuss risk factors of ARIA and highlight important areas for further research. With more anti-amyloid monoclonal antibodies approved by the Food and Drug Administration, considering patient risk factors for developing ARIA is important to identify to minimize patient's risk while receiving these new therapies.

Clinical Markers for Small Vessel Pathology in Alzheimer’s Disease

Background:White matter hyperintensities (WMH) and cerebral microhemorrhages (MH) are common small vessel pathologies that often co-occur with hallmarks of Alzheimer’s Disease (AD) including amyloid-β and tau deposition, neurodegeneration, and decreased cognition. We investigated the relationship among these pathologies to better understand their roles in AD pathogenesis.&#x0D; Methods:A sample from the AD Neuroimaging Initiative (ADNI) with baseline WMH volume WMHV), MH counts, and serum lipids measurements using the Nightingale Health metabolomics platform included cognitively normal, mild cognitive impairment, and AD participants. Spearman rank correlations coefficient and rank regression models were generated to assess the relationship between vascular pathology and mean arterial pressure (MAP), history of hypertension, and serum biomarkers. Models were covaried for age, sex, APOE status, BMI, and years of education. Further analysis was conducted by dividing participants based on APOE status. False discovery rate was controlled by the Benjamini-Hochberg method.&#x0D; Results:WMHV and MH were weakly positively associated (ρ=0.197, p&lt;1*10-10). MH and MAP were positively correlated (p&lt;.05), but MH was not related to history of hypertension, or serum lipids. WMHV was negatively associated with serum VLDL cholesterol (p&lt;1*10-12), LDL cholesterol (p&lt;.0001), and remnant cholesterol (p&lt;1*10-11). In APOE4 carriers only, WMHV was negatively associated with triglycerides (p&lt;.001) and total fatty acids (p&lt;.001), and positively associated with HDL cholesterol (p&lt;.002). WMHV was not related to MAP or history of hypertension.&#x0D; Conclusion:Vascular imaging markers have distinct risk factors with lipid profiles most associated with WMH burden, whereas MAP was predictive of MH. Counterintuitively, lipids associated with higher risk of systemic vascular pathology appeared protective against WMH in the ADNI sample. This phenomenon was particularly notable in APOE4 carriers. Further investigation should be conducted to better understand the relationship between serum lipids and small vessel pathology, and how these contribute to AD pathogenesis.

N-3 PUFA ameliorate functional outcomes following repetitive mTBI in the fat-1 mouse model.

Repeated mild traumatic brain injuries (mTBI) are a continuing healthcare concern worldwide, given its potential for enduring adverse neurodegenerative conditions. Past research suggests a potential protective effect of n-3 polyunsaturated fatty acids (PUFA) in experimental models of mTBI. The aim of this study was to investigate whether the neuroprotective benefits of n-3 PUFA persist following repetitive weight drop injury (WDI). Male fat-1 mice (n = 12), able to endogenously convert n-6 PUFA to n-3 PUFA, and their wild type (WT) counterparts (n = 12) were maintained on a 10% w/w safflower diet. At 9-10 weeks of age, both groups received one mild low-impact WDI on the closed cranium daily, for three consecutive days. Following each WDI, time to righting reflex and seeking behaviour were measured. Neurological recovery, cognitive, motor, and neurobehavioural outcomes were assessed using the Neurological Severity Score (NSS) over 7 days (168 h) post-last WDI. Brains were assessed for cerebral microhemorrhages by Prussian blue and cellular damage by glial fibrillary acidic protein (GFAP) staining. Fat-1 mice exhibited significantly faster righting reflex and seeking behaviour time, and lower mean NSS scores and at all post-WDI time points (p ≤ 0.05) compared to WT mice. Immunohistochemistry showed no significant difference in presence of cerebral microhemorrhage however, fat-1 mice had significantly lower GFAP staining in comparison to WT mice (p ≤ 0.05). n-3 PUFA is effective in restoring cognitive, motor, and behavioural function after repetitive WDI, which may be mediated through reduced cellular damage of the brain.

Cerebral Proteomic Changes in the rTg-D Rat Model of Cerebral Amyloid Angiopathy Type-2 With Cortical Microhemorrhages and Cognitive Impairments.

Cerebral amyloid angiopathy (CAA) is a common disorder of the elderly, a prominent comorbidity of Alzheimer's disease, and causes vascular cognitive impairment and dementia. Previously, we generated a novel transgenic rat model (rTg-D) that produces human familial CAA Dutch E22Q mutant amyloid β-protein (Aβ) in brain and develops arteriolar CAA type-2. Here, we show that deposition of fibrillar Aβ promotes arteriolar smooth muscle cell loss and cerebral microhemorrhages that can be detected by magnetic resonance imaging and confirmed by histopathology. Aged rTg-D rats also present with cognitive deficits. Cerebral proteomic analyses revealed 241 proteins that were significantly elevated with an increase of >50% in rTg-D rats presenting with CAA compared to wild-type rats. Fewer proteins were significantly decreased in rTg-D rats. Of note, high temperature requirement peptidase A (HTRA1), a proteinase linked to transforming growth factor beta 1 (TGF-β1) signaling, was elevated and found to accumulate in cerebral vessels harboring amyloid deposits. Pathway analysis indicated elevation of the TGF-β1 pathway and increased TGF-β1 levels were detected in rTg-D rats. In conclusion, the present findings provide new molecular insights into the pathogenesis of CAA and suggest a role for interactions between HTRA1 and TGF-β1 in the disease process.

Review Of Cerebral Microbleeds using FAZEKA Classification

Introduction: Cerebral microbleeds (CMBs), also known as cerebral microhemorrhages, are tiny hypointense foci discovered by susceptibility-weighted (SW) magnetic resonance imaging (MR). CMBs have been interpreted as asymptomatic lesions that may be identified by chance during a brain MRI. This study was done to understand the etiology and various imaging patterns of the cerebral microbleeds on MRI Materials &amp; Methods: This study was done with a sample size of 325 patients who underwent MRI Brain and diagnosed with CMB at our hospital. Detailed supportive history was taken and data was analysed. Results: Present study shows strong correlation between CMB’s and white matter changes. CMBs in parietal lobe found to have correlation with cognitive dysfunction. Lacunar infract is the most common subtype associated with the CMB’s Conclusion: The markers of microangiopathy on MRI brain are CMBs and white matter changes. Correlation of lobar CMBs with periventricular white matter hyperintensities and deep, infratentorial CMBs with deep white matter hyperintensities were found.

Influence of rehabilitation nursing intervention on blood pressure control and quality of life of elderly patients with hypertension in general practice

Hypertensive cerebral hemorrhage is a typical cerebral microhemorrhage. Due to severe brain injury, the physiological conduction of nerve fibers is interrupted, and clinical symptoms lead to local nerve defects, such as dizziness, headache, disturbance of consciousness, aphasia, and hemiplegia. In recent years, with the improvement of medical level, the mortality rate of hypertensive cerebral hemorrhage has decreased significantly. However, disability rates in long-term clinical studies of survival suggest that rehabilitation measures have a significant impact on promoting the recovery of neurological function.