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Previously, we reported an immediate emergence of new lower jaw input to the anterior forepaw barrel subfield (FBS) in primary somatosensory cortex (SI) following forelimb deafferentation. However, a delay of 7 weeks or more post‐amputation results in the presence of this new input to both anterior and posterior FBS. The immediate change suggests pre‐existing latent lower jaw input in the FBS, whereas the delayed alteration implies the involvement of alternative sources. One possible source for immediate lower jaw responses is the neighboring lower jaw barrel subfield (LJBSF). We used anatomical tracers to investigate the possible projection of LJBSF to the FBS in normal and forelimb‐amputated rats. Our findings are as follows: (1) anterograde tracer injection into LJBSF in normal and amputated rats labeled fibers and terminals exclusively in the anterior FBS; (2) retrograde tracer injection in the anterior FBS in normal and forelimb‐amputated rats, heavily labeled cell bodies predominantly in the posterior LJBSF, with fewer in the anterior LJBSF; (3) retrograde tracer injection in the posterior FBS in normal and forelimb‐amputated rats, sparsely labeled cell bodies in the posterior LJBSF; (4) retrograde tracer injection in anterior and posterior FBS in normal and forelimb‐amputated rats, labeled cells exclusively in ventral posterior lateral (VPL) nucleus and posterior thalamus (PO); (5) retrograde tracer injection in LJBSF‐labeled cell bodies exclusively in ventral posterior medial thalamic nucleus and PO. These findings suggest that LJBSF facilitates rapid lower jaw reorganization in the anterior FBS, whereas VPL and/or other subcortical sites provide a likely substrate for delayed reorganization observed in the posterior FBS. [ABSTRACT FROM AUTHOR]

Introduction Amputations cause changes in both the PNS and CNS, including the emergence of phantom limb sensations (PLS), characterized by the feeling that the amputated limb is still present. Most [...], Following amputation, most amputees still report feeling the missing limb and often describe these feelings as excruciatingly painful. Phantom limb sensations (PLS) are useful while controlling a prosthesis; however, phantom limb pain (PLP) is a debilitating condition that drastically hinders quality of life. Although such experiences have been reported since the early 16th century, the etiology remains unknown. Debate continues regarding the roles of the central and peripheral nervous systems. Currently, the most posited mechanistic theories rely on neuronal network reorganization; however, greater consideration should be given to the role of the dorsal root ganglion within the peripheral nervous system. This Review provides an overview of the proposed mechanistic theories as well as an overview of various treatments for PLP.

We used the forepaw barrel subfield (FBS), that normally receives input from the forepaw skin surface, in rat primary somatosensory cortex as a model system to study rapid and delayed lower jaw‐to‐forepaw cortical reorganization. Single and multi‐unit recording from FBS neurons was used to examine the FBS for the presence of "new" lower jaw input following deafferentations that include forelimb amputation, brachial plexus nerve cut, and brachial plexus anesthesia. The major findings are as follows: (1) immediately following forelimb deafferentations, new input from the lower jaw becomes expressed in the anterior FBS; (2) 7–27 weeks after forelimb amputation, new input from the lower jaw is expressed in both anterior and posterior FBS; (3) evoked response latencies recorded in the deafferented FBS following electrical stimulation of the lower jaw skin surface are significantly longer in both rapid and delayed deafferents compared to control latencies for input from the forepaw to reach the FBS or for input from lower jaw to reach the LJBSF; (4) the longer latencies suggest that an additional relay site is imposed along the somatosensory pathway for lower jaw input to access the deafferented FBS. We conclude that different sources of input and different mechanisms underlie rapid and delayed reorganization in the FBS and suggest that these findings are relevant, as an initial step, for developing a rodent animal model to investigate phantom limb phenomena. [ABSTRACT FROM AUTHOR]

Introduction Antioxidants that decrease cardiovascular risk factors and improve endothelial function (1) are recommended to prevent and treat cardiovascular disease (CVD) and diabetes. (2,3) Ethylene diamine tetraacetic acid (EDTA) chelation [...], Chelation therapy is thought to not only remove contaminating metals but also to decrease free radical production. However, in standard ethylene diamine tetraacetic acid (EDTA) chelation therapy, high doses of vitamin C with potential pro-oxidant effects are often added to the chelation solution. The authors demonstrated previously that the intravenous administration of the standard chelation cocktail, containing high amounts of vitamin C, resulted in an acute transitory pro-oxidant burst that should be avoided in the treatment of pathologies at risk of increased oxidative stress such as diabetes and cardiovascular disease. The current study was designed to determine the acute and chronic biochemical effects of chelation therapy on accepted clinical, antioxidant variables. An EDTA chelation cocktail not containing ascorbic acid was administered to six adult patients for five weeks (10 sessions of chelation therapy); antioxidant indicators were monitored. Immediately after the initial chelation session, in contrast with the data previously reported with the standard cocktail containing high doses of vitamin C, none of the oxidative stress markers were adversely modified. After five weeks, plasma peroxide levels, monitored by malondialdehyde, decreased by 20 percent, and DNA damage, monitored by formamidopyrimidine-DNA glycosylase (Fpg) sensitive sites, decreased by 22 percent. Remaining antioxidant-related variables did not change. In summary, this study demonstrates that multiple sessions of EDTA chelation therapy in combination with vitamins and minerals, but without added ascorbic acid, decreases oxidative stress. These results should be beneficial in the treatment of diseases associated with increased oxidative stress such as diabetes and cardiovascular diseases. (Altern Med Rev 2009;14(1):56-61)

B.1.1.7 is a recently discovered variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with increased transmissibility. Recent findings indicate that this variant has a propensity to infect adolescents and children at higher rates than adults. The virus gains entry into various body cells utilizing angiotensin-converting enzyme 2 (ACE-2) and basigin (CD147) as receptors. The virus mainly affects type II pneumocytes of lungs, endothelial cells, enterocytes, and renal tubular cells. It is reported to affect testes, causing testicular pain, and producing histopathological changes, as observed in some autopsies. The B.1.1.7 variant can also affect various cells in the testes. This raises a major concern regarding the long-term effects of the viral infection on spermatogenesis and highlights the pressing need for a robust database of serum samples from infected male children. [ABSTRACT FROM AUTHOR]

Abstract Background Quantitative trait locus (QTL) mapping is an important tool for identifying potential candidate genes linked to complex traits. QTL mapping has been used to identify genes associated with cytoarchitecture, cell number, brain size, and brain volume. Previously, QTL mapping was utilized to examine variation of barrel field size in the somatosensory cortex in a limited number of recombinant inbred (RI) strains of mice. In order to further elucidate the underlying natural variation in mouse primary somatosensory cortex, we measured the size of the posterior medial barrel subfield (PMBSF), associated with the representation of the large mystacial vibrissae, in an expanded sample set that included 42 BXD RI strains, two parental strains (C57BL/6J and DBA/2J), and one F1 strain (B6D2F1). Cytochrome oxidase labeling was used to visualize barrels within the PMBSF. Results We observed a 33% difference between the largest and smallest BXD RI strains with continuous variation in-between. Using QTL linkage analysis from WebQTL, we generated linkage maps of raw total PMBSF and brain weight adjusted total PMBSF areas. After removing the effects of brain weight, we detected a suggestive QTL (likelihood ratio statistic [LRS]: 14.20) on the proximal arm of chromosome 4. Candidate genes under the suggestive QTL peak for PMBSF area were selected based on the number of single nucleotide polymorphisms (SNPs) present and the biological relevance of each gene. Among the candidate genes are Car8 and Rab2. More importantly, mRNA expression profiles obtained using GeneNetwork indicated a strong correlation between total PMBSF area and two genes (Adcy1 and Gap43) known to be important in mouse cortex development. GAP43 has been shown to be critical during neurodevelopment of the somatosensory cortex, while knockout Adcy1 mice have disrupted barrel field patterns. Conclusion We detected a novel suggestive QTL on chromosome 4 that is linked to PMBSF size. The present study is an important step towards identifying genes underlying the size and possible development of cortical structures.

Barrel subfields in rodent primary somatosensory cortex (SI) are important model systems for studying cortical organization and reorganization. During cortical reorganization that follows limb deafferentation, neurons in deafferented forelimb SI become responsive to previously unexpressed inputs from the lower jaw. Although the lower jaw barrel subfield (LJBSF) is a likely source of the input, this subfield has received little attention. Our aim was to describe the structural and functional organization of the normal LJBSF. To investigate LJBSF organization, a nomenclature for lower jaw skin surface was developed, cytochrome oxidase (CO) was used to label flattened‐cut LJBSF sections, microelectrodes were used to map the lower jaw skin surface representation in SI, and electrolytic lesions, recovered from electrode penetrations, were used to align the physiological map to the underlying barrel map. LJBSF is a tear‐shaped subfield containing approximately 24 barrels, arranged in eight mediolateral rows and a barrel‐free zone capping the anterior border. The representation of the lower jaw skin consisting of chin vibrissae and microvibrissae embedded in common fur is somatotopically organized in a single map in the contralateral SI. This physiological map shows that the activity from the vibrissae aligns with the CO‐staining of the underlying LJBSF. LJBSF barrels receive topographically ordered barrel‐specific input from individual vibrissa and microvibrissae in the lower jaw but not from trident whiskers. The barrel‐free zone receives topographically ordered input from the lower lip. These data demonstrating that the LJBSF is a highly organized subfield are essential for understanding its possible role in cortical reorganization. [ABSTRACT FROM AUTHOR]

Unilateral major limb amputation causes changes in sensory perception. Changes may occur within not only the residual limb but also the intact limb as well as the brain. We tested the hypothesis that limb amputation may result in the detection of hand sensation during stimulation of a non-limb-related body region. We further investigated the responses of unilateral upper limb amputees and individuals with all limbs intact to temporally based sensory tactile testing of the fingertips to test the hypothesis that changes in sensory perception also have an effect on the intact limb. Upper extremity amputees were assessed for the presence of referred sensations (RSs)--experiencing feelings in the missing limb when a different body region is stimulated, to determine changes within the brain that occur due to an amputation. Eight of 19 amputees (42.1%) experienced RS in the phantom limb with manual tactile mapping on various regions of the face. There was no correlation between whether someone had phantom sensations or phantom limb pain and where RS was found. Six of the amputees had either phantom sensation or pain in addition to RS induced by facial stimulation. Results from the tactile testing showed that there were no significant differences in the accuracy of participants in the temporal order judgment tasks (p = 0.702), whereby participants selected the digit that was tapped first by a tracking paradigm that resulted in correct answers leading to shorter interstimulus intervals (ISIs) and incorrect answers increasing the ISI. There were also no significant differences in timing perception, i.e., the threshold accuracy of the duration discrimination task (p = 0.727), in which participants tracked which of the two digits received a longer stimulus. We conclude that many, but not all, unilateral upper limb amputees experience phantom hand sensation and/or pain with stimulation of the face, suggesting that there could be postamputation changes in neuronal circuitry in somatosensory cortex. However, major unilateral limb amputation does not lead to changes in temporal order judgment or timing perception tasks administered via the tactile modality of the intact hand in upper limb amputees. [ABSTRACT FROM AUTHOR]

Background: Quantitative trait locus (QTL) mapping is an important tool for identifying potential candidate genes linked to complex traits. QTL mapping has been used to identify genes associated with cytoarchitecture, cell number, brain size, and brain volume. Previously, QTL mapping was utilized to examine variation of barrel field size in the somatosensory cortex in a limited number of recombinant inbred (RI) strains of mice. In order to further elucidate the underlying natural variation in mouse primary somatosensory cortex, we measured the size of the posterior medial barrel subfield (PMBSF), associated with the representation of the large mystacial vibrissae, in an expanded sample set that included 42 BXD RI strains, two parental strains (C57BL/6J and DBA/2J), and one F1 strain (B6D2F1). Cytochrome oxidase labeling was used to visualize barrels within the PMBSF. Results: We observed a 33% difference between the largest and smallest BXD RI strains with continuous variation in-between. Using QTL linkage analysis from WebQTL, we generated linkage maps of raw total PMBSF and brain weight adjusted total PMBSF areas. After removing the effects of brain weight, we detected a suggestive QTL (likelihood ratio statistic [LRS]: 14.20) on the proximal arm of chromosome 4. Candidate genes under the suggestive QTL peak for PMBSF area were selected based on the number of single nucleotide polymorphisms (SNPs) present and the biological relevance of each gene. Among the candidate genes are Car8 and Rab2. More importantly, mRNA expression profiles obtained using GeneNetwork indicated a strong correlation between total PMBSF area and two genes (Adcy1 and Gap43) known to be important in mouse cortex development. GAP43 has been shown to be critical during neurodevelopment of the somatosensory cortex, while knockout Adcy1 mice have disrupted barrel field patterns. Conclusion: We detected a novel suggestive QTL on chromosome 4 that is linked to PMBSF size. The present study is an important step towards identifying genes underlying the size and possible development of cortical structures. [ABSTRACT FROM AUTHOR]

We measured the combined area of posterior medial barrel subfield (PMBSF) and anterior lateral barrel subfield (ALBSF) areas in four common inbred strains (C3H/HeJ, A  /J, C57BL  /6J, DBA/2J), B6D2F1, and ten recombinant inbred (RI) strains generated from C57BL/6J and DBA/2J progenitors (BXD) as an initial attempt to examine the genetic influences underlying natural variation in barrel field size in adult mice. These two subfields are associated with the representation of the whisker pad and sinus hairs on the contralateral face. Using cytochrome oxidase labeling to visualize the barrel field, we measured the size of the combined subfields in each mouse strain. We also measured body weight and brain weight in each strain. We report that DBA/2J mice have a larger combined PMBSF/ALBSF area (6.15  ±  0.10  mm 2 ,   n   =  7) than C57BL  /6J (5.48  ±  0.13  mm 2 ,   n   =  10), C3H/HeJ (5.37  ±  0.16  mm 2 ,   n   =  10), and A/J mice (5.04  ±  0.09  mm 2 ,   n   =  15), despite the fact that DBA/2J mice have smaller average brain and body sizes. This finding may reflect dissociation between systems that control brain size with those that regulate barrel field area. In addition, BXD strains (average n   =  4) and parental strains showed considerable and continuous variation in PMBSF/ALBSF area, suggesting that this trait is polygenic. Furthermore, brain, body, and cortex weights have heritable differences between inbred strains and among BXD strains. PMBSF/ALBSF pattern appears similar among inbred and BXD strains, suggesting that somatosensory patterning reflects a common plan of organization. This data is an important first step in the quantitative genetic analysis of the parcellation of neocortex into diverse cytoarchitectonic zones that vary widely within and between species, and in identifying the genetic factors underlying barrel field size using quantitative trait locus (QTL) analyses. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) is a promising, non-invasive approach in the diagnosis and treatment of several neurological conditions. However, the specific results in the cortex of the magnitude and spatial distribution of the secondary electrical field (E-field) resulting from TMS at different stimulation sites/orientations and varied TMS parameters are not clearly understood. The objective of this study is to identify the impact of TMS stimulation site and coil orientation on the induced E-field, including spatial distribution and the volume of activation in the cortex across brain areas, and hence demonstrate the need for customized optimization, using a three-dimensional finite element model (FEM). A considerable difference was noted in E-field values and distribution at different brain areas. We observed that the volume of activated cortex varied from 3000 to 7000 mm3 between the selected nine clinically relevant coil locations. Coil orientation also changed the induced E-field by a maximum of 10%, and we noted the least optimal values at the standard coil orientation pointing to the nose. The volume of gray matter activated varied by 10% on average between stimulation sites in homologous brain areas in the two hemispheres of the brain. This FEM simulation model clearly demonstrates the importance of TMS parameters for optimal results in clinically relevant brain areas. The results show that TMS parameters cannot be interchangeably used between individuals, hemispheres, and brain areas. The focality of the TMS induced E-field along with its optimal magnitude should be considered as critical TMS parameters that should be individually optimized. [ABSTRACT FROM AUTHOR]

Offers the author's suggestions on how to promote neuroscience research in Kenya. Encouragement to neuroscientists to do short-term sabbaticals; Initiation of collaborative research which necessitate interactions and travel between individuals in well-established laboratories; Establishment of distant learning centers.

Abstract: Children with fetal alcohol spectrum disorder (FASD) often exhibit sensorimotor dysfunctions that include deficits in motor coordination and fine motor control. Although the underlying causes for these motor abnormalities are unknown, they likely involve interactions between sensory and motor systems. Rodent animal models have been used to study the effects of prenatal alcohol exposure (PAE) on skilled reaching and on the development and organization of somatosensory barrel field cortex. To this end, PAE delayed the development of somatosensory cortex, reduced the size of whisker and forelimb representations in somatosensory barrel field cortex, and delayed acquisition time to learn a skilled reaching task. However, whether PAE also affects the motor cortex (MI) remains to be determined. In the present study, we investigated the effect of PAE on the size of the forelimb representation in rat MI, thresholds for activation, and the overlap between motor and sensory cortical forelimb maps in sensorimotor cortex. Pregnant Sprague–Dawley rats were assigned to alcohol (Alc), pair-fed (PF), and chow-fed (CF) groups on gestation day 1 (GD1). Rats in the Alc group (n =4) were chronically intubated daily with binge doses of alcohol (6g/kg body weight) from GD1 to GD20 that resulted in averaged blood alcohol levels measured on GD10 (mean=191.5±41.9mg/dL) and on GD17 (mean=247.0±72.4mg/dL). PF (n =2) and CF (n =3) groups of pregnant rats served as controls. The effect of PAE on the various dependent measures was obtained from multiple male offspring from each dam within treatment groups, and litter means were compared between the groups from alcohol-treated and control (Ct: CF and PF) dams. At approximately 8 weeks of age, rats were anesthetized with ketamine/xylazine and the skull opened over sensorimotor cortex. A tungsten microelectrode was then inserted into the depths of layer V and intracortical microstimulation was used to deliver trains of pulses to evoke muscle contractions and/or movements; maximum stimulating ≤100μA. When a motor response was observed, the threshold for movement was measured and the motor receptive field projected to the cortical surface to serve as representative point for that location. A motor map for the forelimb representation was generated by systematically stimulating at adjacent sites until current thresholds reached the maximum and/or motor responses were no longer evoked. The major findings in this study were as follows: (1) PAE significantly reduced the area of the forelimb representation in the Alc offspring (6.01mm2, standard error of the mean=±0.278) compared with the Ct offspring (8.03mm2 ±0.586), (2) PAE did not significantly reduce the averaged threshold for activation of movements between groups, (3) PAE significantly reduced the percent overlap (Alc=31.1%, Ct=55.4%) between the forelimb representation in sensory and motor cortices, and (4) no significant differences were observed in averaged body weight, hemisphere weight, or age of animal between treatment groups. These findings suggest that the effects of PAE are not restricted to somatosensory barrel field cortex but also involve the MI and may underlie deficits in motor control and sensorimotor integration observed among children with FASD. [Copyright &y& Elsevier]