Regeneration in the adult Drosophila brain

2020 ◽  
Author(s):  
Kassi L. Crocker ◽  
Khailee Marischuk ◽  
Stacey A. Rimkus ◽  
Hong Zhou ◽  
Jerry C.P. Yin ◽  
...  
Keyword(s):  
Brain Injury ◽  
Brain Regions ◽  
Neural Regeneration ◽  
Cellular Mechanisms ◽  
Proliferating Cells ◽  
Post Injury ◽  
Central Brain ◽  
Drosophila Brain ◽  
Functional Regeneration ◽  
Penetrating Traumatic Brain Injury

AbstractUnderstanding the molecular and cellular mechanisms underlying neurogenesis after injury is crucial for developing tools for brain repair. We have established an adult Drosophila melanogaster model for investigating regeneration after central brain injury. Within 24 hours after Penetrating Traumatic Brain Injury (PTBI) to the central brain, we observe a significant increase in the number of proliferating cells. Between one- and two-weeks post-injury, we detect the generation of new neurons and glia and the formation of new axon tracts that target appropriate brain regions, suggesting there could be functional regeneration. Consistent with functional regeneration, locomotion abnormalities observed shortly after PTBI are largely reversed within 2 weeks of injury. Further, we find that cells surrounding the injury site upregulate neuroblast genes, such as asense and deadpan, and demonstrate that these cells give rise to the new neurons and glia. Taken together, our data support the hypothesis that young, adult Drosophila brains are capable of neuronal repair after central brain injury. We anticipate that our model will facilitate the dissection of the mechanisms of neural regeneration and anticipate that these processes will have relevance to humans.

scholarly journals Neurogenesis in the adult Drosophila brain

Genetics ◽  
2021 ◽  
Author(s):  
Kassi L Crocker ◽  
Khailee Marischuk ◽  
Stacey A Rimkus ◽  
Hong Zhou ◽  
Jerry C P Yin ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurodegenerative Diseases ◽  
Glial Cells ◽  
Brain Regions ◽  
Adult Brain ◽  
Neural Regeneration ◽  
Proliferating Cells ◽  
Brain Regeneration ◽  
Adult Drosophila

Abstract Neurodegenerative diseases such as Alzheimer’s and Parkinson’s currently affect ∼25 million people worldwide (Erkkinen et al. 2018). The global incidence of traumatic brain injury (TBI) is estimated at ∼70 million/year (Dewan et al. 2018). Both neurodegenerative diseases and TBI remain without effective treatments. We are utilizing adult Drosophila melanogaster to investigate the mechanisms of brain regeneration with the long term goal of identifying targets for neural regenerative therapies. We specifically focused on neurogenesis, i.e. the generation of new cells, as opposed to the regrowth of specific subcellular structures such as axons. Like mammals, Drosophila have few proliferating cells in the adult brain. Nonetheless, within 24 hours of a Penetrating Traumatic Brain Injury (PTBI) to the central brain, there is a significant increase in the number of proliferating cells. We subsequently detect both new glia and new neurons and the formation of new axon tracts that target appropriate brain regions. Glial cells divide rapidly upon injury to give rise to new glial cells. Other cells near the injury site upregulate neural progenitor genes including asense and deadpan and later give rise to the new neurons. Locomotor abnormalities observed after PTBI are reversed within two weeks of injury, supporting the idea that there is functional recovery. Together, these data indicate that adult Drosophila brains are capable of neuronal repair. We anticipate that this paradigm will facilitate the dissection of the mechanisms of neural regeneration and that these processes will be relevant to human brain repair.

scholarly journals Connectomic Assessment of Injury Burden and Longitudinal Structural Network Alterations in Moderate-to-severe Traumatic Brain Injury

2021 ◽  
Author(s):  
Yusuf Osmanlioglu ◽  
Drew Parker ◽  
Jacob A Alappatt ◽  
James J Gugger ◽  
Ramon R Diaz-Arrastia ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Structural Connectivity ◽  
Public Health Problem ◽  
Brain Regions ◽  
Brain Network ◽  
Major Public Health Problem ◽  
Post Injury ◽  
Structural Network ◽  
Injury Burden

Traumatic brain injury (TBI) is a major public health problem. Caused by external mechanical forces, a major characteristic of TBI is the shearing of axons across the white matter, which causes structural connectivity disruptions between brain regions. This diffuse injury leads to cognitive deficits, frequently requiring rehabilitation. Heterogeneity is another characteristic of TBI as severity and cognitive sequelae of the disease have a wide variation across patients, posing a big challenge for treatment. Thus, measures assessing network-wide structural connectivity disruptions in TBI are necessary to quantify injury burden of individuals, which would help in achieving personalized treatment, patient monitoring, and rehabilitation planning. Despite TBI being a disconnectivity syndrome, connectomic assessment of structural disconnectivity has been very scarce. In this study, we propose a novel connectomic measure that we call network anomaly score (NAS) to capture the integrity of structural connectivity in TBI patients by leveraging two major characteristics of the disease: diffuseness of axonal injury and heterogeneity of the disease. Over a longitudinal cohort of moderate-to-severe TBI patients, we demonstrate that structural network topology of patients are more heterogeneous and are significantly different than that of healthy controls at 3 months post-injury, where dissimilarity further increases up to 12 months. We also show that NAS captures injury burden as quantified by post-traumatic amnesia and that alterations in the structural brain network is not related to cognitive recovery. Finally we compare NAS to major graph theory measures used in TBI literature and demonstrate the superiority of NAS in characterizing the disease.

scholarly journals Effects of Traumatic Brain Injury on Regional Cerebral Blood Flow in Rats as Measured with Radiolabeled Microspheres

1989 ◽  
Vol 9 (1) ◽  
pp. 117-124 ◽  
Author(s):  
Iwao Yamakami ◽  
Tracy K. McIntosh
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Regions ◽  
Post Injury ◽  
Fluid Percussion ◽  
Hemodynamic Variables ◽  
Acute Changes ◽  
Injury Recovery ◽  
Left Parietal Cortex ◽  
Experimental Traumatic Brain Injury

To clarify the effect of experimental brain injury on regional CBF (rCBF), repeated rCBF measurements were performed using radiolabeled microspheres in rats Subjected to fluid-percussion traumatic brain injury. Three consecutive microsphere injections in six uninjured control rats substantiated that the procedure induces no significant changes in hemodynamic variables or rCBF. Animals were subjected to left parietal fluid-percussion brain injury of moderate severity (2.1–2.4 atm) and rCBF values were determined (a) prior to injury and 15 min and 1 h following injury (n = 7); and (b) prior to injury and 30 min and 2 h following injury (n = 7). At 15 min post injury, there was a profound reduction of rCBF in all brain regions studied (p < 0.01). Although rCBF in the hindbrain had recovered to near-normal by 30 min post injury, rCBF in both injured and contralateral (uninjured) forebrain areas remained significantly suppressed up to 1 h post injury. At 2 h post injury, recovery of rCBF to near-normal values was observed in all brain regions except the focal area of injury (left parietal cortex) where rCBF remained significantly depressed (p < 0.01). This prolonged focal oligemia at the injury site was associated with the development of reproducible cystic necrosis in the left parietotemporal cortex at 4 weeks post injury. Our results demonstrate that acute changes in rCBF occur following experimental traumatic brain injury in rats and that rCBF remains significantly depressed up to 2 h post injury in the area circumscribing the trauma site.

scholarly journals New lymphatic cell formation is associated with damaged brain tissue clearance after penetrating traumatic brain injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fan-Wei Meng ◽  
Jun-Tao Yu ◽  
Jin-Yuan Chen ◽  
Peng-Fei Yang
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Tissue ◽  
Tissue Repair ◽  
Cell Formation ◽  
Post Injury ◽  
Cd34 Antigen ◽  
Clearance Mechanism ◽  
Specific Pathogen ◽  
Penetrating Traumatic Brain Injury

AbstractWe characterized the tissue repair response after penetrating traumatic brain injury (pTBI) in this study. Seventy specific pathogen-free Kunming mice were randomly divided into the following groups: normal control, 1, 3, 7, 15, 21, and 30 days after pTBI. Hematoxylin and eosin (H&E) staining, immunohistochemistry, and immunofluorescence were performed to examine and monitor brain tissue morphology, and the distribution and expression of lymphatic-specific markers lymphatic vessel endothelial receptor-1 (LYVE-1), hematopoietic precursor cluster of differentiation 34 (CD34) antigen, and Prospero-related homeobox-1 (PROX1) protein. H&E staining revealed that damaged and necrotic tissues observed on day 1 at and around the injury site disappeared on day 7, and there was gradual shrinkage and disappearance of the lesion on day 30, suggesting a clearance mechanism. We explored the possibility of lymphangiogenesis causing this clearance as part of the post-injury response. Notably, expression of lymphangiogenesis markers LYVE-1, CD34, and PROX1 was detected in damaged mouse brain tissue but not in normal tissue. Moreover, new lymphatic cells and colocalization of LYVE-1/CD34 and LYVE-1/PROX1 were also observed. Our findings of the formation of new lymphatic cells following pTBI provide preliminary insights into a post-injury clearance mechanism in the brain. Although we showed that lymphatic cells are implicated in brain tissue repair, further research is required to clarify the origin of these cells.

scholarly journals Diffuse Brain Injury Elevates Tonic Glutamate Levels and Potassium-Evoked Glutamate Release in Discrete Brain Regions at Two Days Post-Injury: An Enzyme-Based Microelectrode Array Study

2010 ◽  
Vol 27 (5) ◽  
pp. 889-899 ◽  
Author(s):  
Jason M. Hinzman ◽  
Theresa Currier Thomas ◽  
Jason J. Burmeister ◽  
Jorge E. Quintero ◽  
Peter Huettl ◽  
...  
Keyword(s):  
Brain Injury ◽  
Microelectrode Array ◽  
Glutamate Release ◽  
Brain Regions ◽  
Post Injury ◽  
Diffuse Brain Injury ◽  
Diffuse Brain

scholarly journals Hippocampal Expression of Cytochrome P450 1B1 in Penetrating Traumatic Brain Injury

2022 ◽  
Vol 23 (2) ◽  
pp. 722
Author(s):  
Erik Lidin ◽  
Mattias K. Sköld ◽  
Maria Angéria ◽  
Johan Davidsson ◽  
Mårten Risling
Keyword(s):  
Traumatic Brain Injury ◽  
Cytochrome P450 ◽  
Brain Injury ◽  
Mrna Expression ◽  
Post Injury ◽  
Cytochrome P450 1B1 ◽  
Sham Surgery ◽  
17Β Estradiol ◽  
Penetrating Traumatic Brain Injury ◽  
Cyp1b1 Mrna

Hippocampal dysfunction contributes to multiple traumatic brain injury sequala. Female rodents’ outcome is superior to male which has been ascribed the neuroprotective sex hormones 17β-estradiol and progesterone. Cytochrome P450 1B1 (CYP1B1) is an oxidative enzyme influencing the neuroinflammatory response by creating inflammatory mediators and metabolizing neuroprotective 17β-estradiol and progesterone. In this study, we aimed to describe hippocampal CYP1B1 mRNA expression, protein presence of CYP1B1 and its key redox partner Cytochrome P450 reductase (CPR) in both sexes, as well as the effect of penetrating traumatic brain injury (pTBI). A total 64 adult Sprague Dawley rats divided by sex received pTBI or sham-surgery and were assigned survival times of 1-, 3-, 5- or 7 days. CYP1B1 mRNA was quantified using in-situ hybridization and immunohistochemistry performed to verify protein colocalization. CYP1B1 mRNA expression was present in all subregions but greatest in CA2 irrespective of sex, survival time or intervention. At 3-, 5- and 7 days post-injury, expression in CA2 was reduced in male rats subjected to pTBI compared to sham-surgery. Females subjected to pTBI instead exhibited increased expression in all CA subregions 3 days post-injury, the only time point expression in CA2 was greater in females than in males. Immunohistochemical analysis confirmed neuronal CYP1B1 protein in all hippocampal subregions, while CPR was limited to CA1 and CA2. CYP1B1 mRNA is constitutively expressed in both sexes. In response to pTBI, females displayed a more urgent but brief regulatory response than males. This indicates there may be sex-dependent differences in CYP1B1 activity, possibly influencing inflammation and neuroprotection in pTBI.

Functional Correlates of Midline Brain Volume Loss in Chronic Traumatic Brain Injury

2015 ◽  
Vol 21 (8) ◽  
pp. 650-655 ◽  
Author(s):  
Emma B. Guild ◽  
Brian Levine
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Regions ◽  
Specific Pattern ◽  
Focal Lesion ◽  
Volume Loss ◽  
Post Injury ◽  
Functional Changes ◽  
Physical Complaints ◽  
Wide Range

AbstractTraumatic brain injury (TBI) is associated with long-term changes in daily life functioning, yet the neuroanatomical correlates of these changes are poorly understood. This study related outcome assessed across several domains to brain structure derived from quantitative magnetic resonance imaging (MRI). Sixty individuals spanning a wide range of TBI severity participated 1-year post-injury as part of the Toronto TBI study. Volumetric data over 38 brain regions were derived from high resolution T1-weighted MRI scans. Functioning was assessed with a battery of self- and significant-other rated measures. Multivariate analysis (partial least squares) was used to identify shared variance between the neuroimaging and outcome measures. TBI was associated with item endorsement on outcome questionnaires without strong evidence for severity or focal lesion effects. Prefrontal midline, cingulate, medial temporal, right inferior parietal and basal ganglia/thalamic volumes were associated with measures of initiative, energization, and physical complaints. In the chronic stage of TBI, self-initiation, energization, and physical complaints related to a specific pattern of volume loss in midline and lateral regions known to be involved in motivation, apathy, and attention. These results suggest that crucial functional changes in chronic TBI may be associated with volume loss in established midline-frontal and attentional circuits. (JINS, 2015,21, 650–655)

scholarly journals Changes in Neuropeptide Y after Experimental Traumatic Brain Injury in the Rat

1992 ◽  
Vol 12 (4) ◽  
pp. 697-702 ◽  
Author(s):  
Tracy K. McIntosh ◽  
Donna Ferriero
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuropeptide Y ◽  
Parietal Cortex ◽  
Brain Regions ◽  
Male Rats ◽  
Post Injury ◽  
Regional Brain ◽  
Left Parietal Cortex ◽  
Experimental Traumatic Brain Injury

We utilized a model of fluid percussion (FP) brain injury in the rat to examine the hypothesis that alterations in brain neuropeptide Y (NPY) concentrations occur following brain injury. Male rats (n = 44) were subjected to FP traumatic brain injury. One group of animals (n = 38) was killed at 1 min, 15 min, 1 h, or 24 h after brain injury, and regional brain homogenates were analyzed for NPY concentrations using radioimmunoassay. A second group of animals (n = 6) was killed for NPY immunocytochemistry. Concentrations of NPY in the injured left parietal cortex were significantly elevated at 15 min post injury (p < 0.05). No changes were observed in other brain regions. NPY-immunoreactive fibers were seen at 15 min post injury predominantly in the injured cortex and adjacent hippocampus. These temporal changes in NPY immunoreactivity, together with previous observations concerning posttraumatic changes in regional CBF in these same areas, suggest that an increase in region NPY concentrations after brain injury may be involved in part in the pathogenesis of posttraumatic hypoperfusion.

P23 Investigating synaptopathy following traumatic brain injury in a preclinical model

2019 ◽  
Vol 90 (3) ◽  
pp. e31.3-e31
Author(s):  
AAB Jamjoom ◽  
Z Qui ◽  
J Rhodes ◽  
PJD Andrews ◽  
SGN Grant
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Pearson Correlation ◽  
Brain Regions ◽  
Machine Learning Algorithms ◽  
Preclinical Model ◽  
Strong Positive Correlation ◽  
Post Injury ◽  
Positive Correlation ◽  
The Impact

ObjectivesThe impact of Traumatic Brain Injury (TBI) on the synapse is poorly understood. We examined the impact of TBI on the distribution of two postsynaptic density proteins (PSD95 and SAP102) at single-synapse resolution.Subjects44 male transgenic knock-in mice, aged 8–16 weeks, expressing fluorescently labelled PSD95 and SAP102.MethodsMice were randomised to a mild lateral fluid percussion injury (LFPI) or sham treatment and brain sections were examined at 7 and 28 days. Using high resolution confocal microscopy and machine learning algorithms, the synaptic puncta density, size and intensity were mapped across 222 brain regions. Microglia and presynaptic changes were indexed using Iba1 and SV2A immunostaining. Pearson correlation and t-tests were used (significance p<0.05).ResultsWe found a significant reduction in synaptic puncta density at 28 days post-injury in brain regions distal to the injury site including the hippocampus. PSD95 and SAP102 density changes had a strong positive correlation at 28 days (r=0.8; p<0.0001). We also observed evidence of synapse recovery in the ipsilateral cortex between 7 and 28 days. Puncta density had a positive correlation with SV2A (r=0.7; p<0.01) and a negative correlation with (r=−0.6; p<0.001) Iba1 count.ConclusionsFocal LFPI induced progressive region-specific loss of synapses for which microglia may play a role. Our study highlights the value of brain-wide synaptome mapping technology and suggests a capacity for synaptic recovery which could be a therapeutic target.

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