Axonal Sprouting in the Adult Brain: Mechanisms of Lesion-Specific Sprouting of the Corticostriatal Pathway in Adult Rats

2005 ◽  
pp. 97-110 ◽  
Keyword(s):  
Adult Brain ◽  
Axonal Sprouting ◽  
Adult Rats

scholarly journals Transfer of rhodamine-123 into the brain and cerebrospinal fluid of fetal, neonatal and adult rats

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Liam M. Koehn ◽  
Katarzyna M. Dziegielewska ◽  
Mark D. Habgood ◽  
Yifan Huang ◽  
Norman R. Saunders
Keyword(s):  
Cerebrospinal Fluid ◽  
Fetal Brain ◽  
Maternal Blood ◽  
Adult Brain ◽  
Rhodamine 123 ◽  
Patient Specific ◽  
Adult Rats ◽  
Blood Brain ◽  
The Brain ◽  
Brain Barriers

Abstract Background Adenosine triphosphate binding cassette transporters such as P-glycoprotein (PGP) play an important role in drug pharmacokinetics by actively effluxing their substrates at barrier interfaces, including the blood-brain, blood-cerebrospinal fluid (CSF) and placental barriers. For a molecule to access the brain during fetal stages it must bypass efflux transporters at both the placental barrier and brain barriers themselves. Following birth, placental protection is no longer present and brain barriers remain the major line of defense. Understanding developmental differences that exist in the transfer of PGP substrates into the brain is important for ensuring that medication regimes are safe and appropriate for all patients. Methods In the present study PGP substrate rhodamine-123 (R123) was injected intraperitoneally into E19 dams, postnatal (P4, P14) and adult rats. Naturally fluorescent properties of R123 were utilized to measure its concentration in blood-plasma, CSF and brain by spectrofluorimetry (Clariostar). Statistical differences in R123 transfer (concentration ratios between tissue and plasma ratios) were determined using Kruskal-Wallis tests with Dunn’s corrections. Results Following maternal injection the transfer of R123 across the E19 placenta from maternal blood to fetal blood was around 20 %. Of the R123 that reached fetal circulation 43 % transferred into brain and 38 % into CSF. The transfer of R123 from blood to brain and CSF was lower in postnatal pups and decreased with age (brain: 43 % at P4, 22 % at P14 and 9 % in adults; CSF: 8 % at P4, 8 % at P14 and 1 % in adults). Transfer from maternal blood across placental and brain barriers into fetal brain was approximately 9 %, similar to the transfer across adult blood-brain barriers (also 9 %). Following birth when placental protection was no longer present, transfer of R123 from blood into the newborn brain was significantly higher than into adult brain (3 fold, p < 0.05). Conclusions Administration of a PGP substrate to infant rats resulted in a higher transfer into the brain than equivalent doses at later stages of life or equivalent maternal doses during gestation. Toxicological testing of PGP substrate drugs should consider the possibility of these patient specific differences in safety analysis.

scholarly journals Region-specific maladaptive gray matter myelination is associated with differential susceptibility to stress-induced behavior in male rodents and humans

2021 ◽  
Author(s):  
Kimberly L. P. Long ◽  
Linda L. Chao ◽  
Yurika Kazama ◽  
Anjile An ◽  
Kelsey Y. Hu ◽  
...  
Keyword(s):  
Gray Matter ◽  
Traumatic Stress ◽  
Adult Brain ◽  
Fear Learning ◽  
Male Rats ◽  
Adult Rats ◽  
Behavioral Variation ◽  
Weighted Estimates ◽  
Functional Changes ◽  
Symptom Profiles

AbstractBackgroundIndividual reactions to traumatic stress vary dramatically, yet the biological basis of this variation remains poorly understood. Recent studies have demonstrated surprising plasticity of oligodendrocytes and myelin in the adult brain, providing a potential mechanism by which aberrant structural and functional changes arise in the brain following trauma exposure.MethodsWe tested the hypothesis that gray matter myelin contributes to traumatic stress-induced behavioral variation. We exposed adult rats to a single, severe stressor and used a multimodal approach to characterize avoidance, startle, and fear-learning behavior. We quantified oligodendrocyte and myelin content in multiple brain areas and compared these measures to behavioral metrics. We then induced overexpression of the oligodendrogenic transcription factor Olig1 in the adult rat dentate gyrus (DG) to test the potential, causal role of oligodendrogenesis in behavioral variation. Lastly, T1-/T2-weighted estimates of myelin were compared to trauma-induced symptom profiles in humans.ResultsOligodendrocytes and myelin in the DG of the hippocampus positively correlated with stress-induced avoidance behaviors in male rats. In contrast, myelin levels in the amygdala positively correlated with contextual fear learning. Olig1 overexpression increased place avoidance compared to control virus animals, indicating that increased oligodendrocyte drive in the DG is sufficient to induce an avoidance behavioral phenotype. Finally, variation in myelin correlated with trauma-induced symptom profiles in humans in a region-specific manner that mirrored our rodent findings.ConclusionsThese results demonstrate a species-independent relationship between region-specific, gray matter oligodendrocytes and myelin and differential behavioral phenotypes following traumatic stress exposure. This study provides a novel biological framework for understanding the mechanisms that underlie individual variance in sensitivity to traumatic stress.

scholarly journals Pattern of chondroitin sulfate proteoglycan expression after ablation of the sensorimotor cortex of the neonatal and adult rat brain

2008 ◽  
Vol 60 (4) ◽  
pp. 581-591
Author(s):  
Sanja Dacic ◽  
Sanja Pekovic ◽  
Maja Stojiljkovic ◽  
Irena Lavrnja ◽  
Danijela Stojkov ◽  
...  
Keyword(s):  
Chondroitin Sulfate ◽  
Rat Brain ◽  
Sensorimotor Cortex ◽  
Immunohistochemical Analysis ◽  
Recovery Process ◽  
Adult Brain ◽  
Sulfate Proteoglycan ◽  
Adult Rats ◽  
Adult Rat ◽  
Adult Rat Brain

The central nervous system has a limited capacity for self-repair after damage. However, the neonatal brain has agreater capacity for recovery than the adult brain. These differences in the regenerative capability depend on local environmental factors and the maturational stage of growing axons. Among molecules which have both growth-promoting and growth-inhibiting activities is the heterogeneous class of chondroitin sulfate proteoglycans (CSPGs). In this paper, we investigated the chondroitin-4 and chondroitin-6 sulfate proteoglycan expression profile after left sensorimotor cortex ablation of the neonatal and adult rat brain. Immunohistochemical analysis revealed that compared to the normal uninjured cortex, lesion provoked up regulation of CSPGs showing a different pattern of expression in the neonatal vs. the adult brain. Punctuate and membrane-bound labeling was predominate after neonatal lesion, where as heavy deposition of staining in the extracellular matrix was observed after adult lesion. Heavy deposition of CSPG immunoreactivity around the lesionsite in adult rats, in contrast to a less CSPG-rich environment in neonatal rats, indicated that enhancement of the recovery process after neonatal injury is due to amore permissive environment.

scholarly journals Meteorin is a Chemokinetic Factor in Neuroblast Migration and Promotes Stroke-Induced Striatal Neurogenesis

2011 ◽  
Vol 32 (2) ◽  
pp. 387-398 ◽  
Author(s):  
Zhaolu Wang ◽  
Nuno Andrade ◽  
Malene Torp ◽  
Somsak Wattananit ◽  
Andreas Arvidsson ◽  
...  
Keyword(s):  
Neural Progenitor Cells ◽  
Apoptotic Cell ◽  
Artery Occlusion ◽  
Adult Brain ◽  
Adult Rats ◽  
Neuroblast Migration ◽  
Mature Neurons ◽  
Cerebral Artery Occlusion

Ischemic stroke affecting the adult brain causes increased progenitor proliferation in the subventricular zone (SVZ) and generation of neuroblasts, which migrate into the damaged striatum and differentiate to mature neurons. Meteorin (METRN), a newly discovered neurotrophic factor, is highly expressed in neural progenitor cells and immature neurons during development, suggesting that it may be involved in neurogenesis. Here, we show that METRN promotes migration of neuroblasts from SVZ explants of postnatal rats and stroke-subjected adult rats via a chemokinetic mechanism, and reduces N-methyl-d-asparate-induced apoptotic cell death in SVZ cells in vitro. Stroke induced by middle cerebral artery occlusion upregulates the expression of endogenous METRN in cells with neuronal phenotype in striatum. Recombinant METRN infused into the stroke-damaged brain stimulates cell proliferation in SVZ, promotes neuroblast migration, and increases the number of immature and mature neurons in the ischemic striatum. Our findings identify METRN as a new factor promoting neurogenesis both in vitro and in vivo by multiple mechanisms. Further work will be needed to translate METRN's actions on endogenous neurogenesis into improved recovery after stroke.

scholarly journals Competition among oxidizable substrates in brains of young and adult rats. Dissociated cells

1984 ◽  
Vol 219 (1) ◽  
pp. 131-135 ◽  
Author(s):  
L M Roeder ◽  
J T Tildon ◽  
D C Holman
Keyword(s):  
Plasma Membranes ◽  
Ketone Bodies ◽  
Age Groups ◽  
Cell Types ◽  
Adult Brain ◽  
Brain Cells ◽  
Adult Rats ◽  
Young Rats ◽  
Dissociated Cells ◽  
14Co2 Production

The rates of conversion of D-(-)-3-hydroxy[3-14C]butyrate, [3-14C]acetoacetate, [6-14C]glucose and [U-14C]glutamine into 14CO2 were measured in the presence and absence of alternative oxidizable substrates in intact dissociated cells from the brains of young and adult rats. When unlabelled glutamine was added to [6-14C]glucose or unlabelled glucose was added to [U-14C]glutamine, the rate of 14CO2 production was decreased in both young and adult rats. The rate of oxidation of 3-hydroxy[3-14C]butyrate was also decreased by the addition of unlabelled glutamine in both age groups, but in the reverse situation, i.e. unlabelled 3-hydroxybutyrate added to [U-14C]glutamine, only the brain cells from young rats were affected. No significant effects were seen when glutamine and acetoacetate were combined. The addition of either of the two ketone bodies to [6-14C]glucose markedly lowered the rate of 14CO2 production in young rats, but in the adult only 3-hydroxybutyrate was effective and the magnitude of decrease in the rate of [6-14C]glucose oxidation was much lower than in young animals. Unlabelled glucose decreased the rate of [3-14C]acetoacetate oxidation to a minor extent in brain cells from both age groups; when added to 3-hydroxy[3-14C]butyrate, glucose had no effect in young rats and greatly enhanced 14CO2 production in adult brain cells. Many of these patterns of substrate interaction in dissociated brain cells differ from those in whole homogenates; they may be a function of the plasma membranes and the role of a carrier-mediated transport system or a reflection of a difference in the population of cell types or subcellular organelles in these two preparations.

scholarly journals The Expression of FOXJ1 in Neurogenesis after Transient Focal Cerebral Ischemia

2013 ◽  
Vol 40 (3) ◽  
pp. 403-409 ◽  
Author(s):  
Yabo Huang ◽  
Zheng Xu ◽  
Jie Cao ◽  
Haibo Cao ◽  
Shiming Zhang
Keyword(s):  
Cerebral Ischemia ◽  
Expression Pattern ◽  
Focal Cerebral Ischemia ◽  
Artery Occlusion ◽  
Adult Brain ◽  
Immunofluorescence Staining ◽  
Double Immunofluorescence ◽  
Adult Rats ◽  
Ischemic Core ◽  
The Brain

Objective and Background:FOXJ1 is a member of the Forkhead/winged-helix (Fox) family of transcription factors, which is required for the differentiation of the cells acting as adult neural stem cells which participate in neurogenesis and give rise to neurons, astrocytes, oligodendrocytes. The expression pattern of FOXJ1 in the brain after cerebral ischemia has so far not been described. In the current study, we investigated the expression pattern of FOXJ1 in the rat brain after cerebral ischemia by animal model.Methods:We performed a middle cerebral artery occlusion (MCAO) model in adult rats and investigated the expression of FOXJ1 in the brain by Western blotting and immunochemistry; double immunofluorescence staining was used to analyze FOXJ1's co-expression with Ki67.Results:Western blot analysis showed that the expression of FOXJ1 was lower than normal and sham-operated brain after cerebral ischemia, but the level of FOXJ1 gradually increased from Day 1 to Day 14. Immuohistochemical staining suggested that the immunostaining of FOXJ1 deposited strongly in the ipsilateral and contralateral hemisphere in the cortical penumbra (CP). There was no FOXJ1 expression in the ischemic core (IC). The positive cells in the cortical penumbra might migrat to the ischemic core. In addition, double immunofluorescence staining revealed that FOXJ1 was co-expressed with mAP-2 and gFAP, and Ki67 had the colocalization with NeuN, GFAP, and FOXJ1.Conclusions:All our findings suggest that FOXJ1 plays an important role on neuronal production and neurogenesis in the adult brain after cerebral ischemia.

Characterization of Mitotic Neurons Derived From Adult Rat Hypothalamus and Brain Stem

2002 ◽  
Vol 87 (2) ◽  
pp. 1076-1085 ◽  
Author(s):  
Jenafer Evans ◽  
Colin Sumners ◽  
Jennifer Moore ◽  
Matthew J. Huentelman ◽  
Jie Deng ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Membrane Potential ◽  
Brain Stem ◽  
Adult Brain ◽  
Neonatal Rat ◽  
Peak Current Density ◽  
Adult Rats ◽  
Peak Current ◽  
Rat Hypothalamus ◽  
Adult Rat

Embryonic or neonatal rat neurons retain plasticity and are readily grown in tissue culture, but neurons of the adult brain were thought to be terminally differentiated and therefore difficult to culture. Recent studies, however, suggest that it may be possible to culture differentiated neurons from the hippocampus of adult rats. We modified these procedures to grow differentiated neurons from adult rat hypothalamus and brain stem. At day 7 in tissue culture and beyond, the predominant cell types in hypothalamic and brain stem cultures had a stellate morphology and could be subdivided into two distinct groups, one of which stained with antibodies to the immature neuron marker α-internexin, while the other stained with the astrocyte marker GFAP. The α-internexin positive cells were mitotic and grew to form a characteristic two-dimensional cellular network. These α-internexin positive cells coimmunostained for the neuronal markers MAP2, type III β-tubulin, and tau, and also bound tetanus toxin, but were negative for the oligodendrocyte marker GalC and also for the neurofilament triplet proteins NF-L, NF-M, and NF-H, markers of more mature neurons. Patch-clamp analysis of these α-internexin positive cells revealed small Ca2+ currents with a peak current of −0.5 ± 0.1 pA/pF at a membrane potential of −20 mV ( n = 5) and half-maximal activation at −30 mV ( n = 5). Na+ currents with a peak current density of −154.5 ± 49.8 pA/pF at a membrane potential of −15 mV ( n = 5) were also present. We also show that these cells can be frozen and regrown in tissue culture and that they can be efficiently infected by viral vectors. These cells therefore have the immunological and electrophysiological properties of immature mitotic neurons and should be useful in a variety of future studies of neuronal differentiation and function.

scholarly journals Competition among oxidizable substrates in brains of young and adult rats. Whole homogenates

1984 ◽  
Vol 219 (1) ◽  
pp. 125-130 ◽  
Author(s):  
L M Roeder ◽  
J T Tildon ◽  
J H Stevenson
Keyword(s):  
Brain Tissue ◽  
Ketone Bodies ◽  
Adult Brain ◽  
Adult Rats ◽  
Young Rats ◽  
Age Dependent ◽  
14Co2 Production ◽  
Presence And Absence

The rates of conversion into 14CO2 of D-(-)-3-hydroxy[3-14C]butyrate, [3-14C]acetoacetate, [6-14C]glucose and [U-14C]glutamine were measured in the presence and absence of unlabelled alternative oxidizable substrates in whole homogenates from the brains of young and adult rats. The addition of unlabelled glutamine resulted in decreased 14CO2 production from [6-14C]glucose in brain homogenates from both young and adult rats. In contrast, glucose had no effect on [U-14C]glutamine oxidation. In suckling animals, both 3-hydroxybutyrate and acetoacetate decreased the rate of oxidation of [6-14C]glucose, but in adults only 3-hydroxybutyrate had an effect, and to a lesser degree. The addition of unlabelled glucose markedly enhanced the rates of oxidation of both ketone bodies in adult brain tissue and had little or no effect in the young. The rate of production of 14CO2 from [U-14C]glutamine was increased by the addition of unlabelled ketone bodies in brain homogenates from young, but not from adult rats. In the converse situation, unlabelled glutamine added to 14C-labelled ketone bodies diminished 14CO2 production in young rats, but had no effect in adult animals. These results revealed a complex age-dependent pattern of interaction in which certain substrates apparently competed with each other, whereas an enhanced rate of 14CO2 production was found with others.

EphA/ephrin-A interactions regulate epileptogenesis and activity-dependent axonal sprouting in adult rats

2003 ◽  
Vol 24 (4) ◽  
pp. 984-999 ◽  
Author(s):  
B Xu ◽  
S Li ◽  
A Brown ◽  
R Gerlai ◽  
M Fahnestock ◽  
...  
Keyword(s):  
Axonal Sprouting ◽  
Adult Rats ◽  
Activity Dependent
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