Spontaneous activity in neuronal networks in vitro is common and has been well documented. However, alteration of spontaneous activity in such networks via conditioning electrical stimulation has received much less experimental attention. Two different patterns of electrical stimulation were used to enhance or depress the level of spontaneous activity in spinal cord cultures. High-frequency stimulation (HFS), a method routinely shown to increase the efficacy of synaptic transmission, was employed to augment spontaneous activity. Low-frequency stimulation (LFS), the technique often applied to depress synaptic efficacy, was employed to decrease spontaneous activity. In addition, LFS was used to reverse the effect of HFS on spontaneous activity. Likewise, HFS was applied to counter the effect of LFS. Because these networks were grown on multi-microelectrode plates (MMEPs), this allowed the simultaneous stimulation of any combination of the 64 electrodes in the array. Thus, the possible differences in response to single versus multi-electrode stimulation were also addressed. Finally, test-pulses were delivered before and after the conditioning stimulation on the same stimulation electrode(s) in order to assess the change in mean evoked action potentials (MEAPs). Dissociated spinal tissue from embryonic mice was allowed to mature into self-organized networks that exhibited spontaneous bursting activity after two weeks of incubation. Spontaneous activity was monitored from up to 14 recording channels simultaneously. Although uniform responses to stimulation across all recording electrodes were rarely observed, a large majority of the recording channels had similar responses. Spontaneous activity was increased in 52% of 89 HFS trials, whereas activity was decreased in 35% of 75 LFS trials. The duration of most of these increases was less than 5 minutes. When there were substantial and long-term (> 15 min) changes in spontaneous activity, the opposing stimulation pattern successfully reversed the effect of the previous stimulation. The percent change in MEAPs following conditioning stimulation suggested that synaptic modification had taken place in 75% of all test-pulse stimulation trials.

Rapid receptive field (RF) reorganization of somatosensory neurons in the rat dorsal horn was examined using extracellular single unit recording. Subcutaneous injection of lidocaine into RFs of dorsal horn neurons results in expansion of their RFs within minutes. The expanded RFs appear adjacent to or/and proximal to original RFs. Out of 63 neurons tested, 36 (58%) show RF reorganization. The data suggest that dorsal horn of spinal cord is one of the initial sites for RF reorganization. The neural mechanisms of this effect are not well understood. We propose that changes in biophysical properties (membrane conductance, length constant) of the neurons resulting from lidocaine injection contribute to RF reorganization. Iontophoretic application of glutamate onto dorsal horn neurons that show lidocaine induced RF's expansion were used to test the model. Application of glutamate produced reduction of reorganized RFs in 9 of 20 (45%) tested cells. Application of NBQX produced no effect on either original or expanded RFs indicate that RF shrinkage effects of glutamate involve NMDA receptors. The results are consistent with the prediction of the proposed model. Subcutaneous injection of capsaicin into tactile RFs of low threshold mechanoreceptive dorsal horn neurons produced no effect on the RF sizes that are consistent with other studies. Following the injection, the original RFs were completely silenced (46%) or remained responsive (54%).

Spinal cord injury (SCI) is a devastating disease which poses health problems in human and veterinary medicine. SCI causes neurological disability, with loss of motor, sensory and autonomic function. This study investigated the efficacy of local treatment with IKVAV-peptide on spinal cord regeneration following compression injury at T12 vertebra in Balb-c mice. IKVAV-peptide is a membrane spanning peptide known to have a long half-life and the peptide motif IKVAV. Thirty Blab-c female mice were used. Hemilaminectomy was performed at T12 and spinal cords were compressed using extradural application of a 24 g modified aneurysm clip for 1 min in the treatment groups. After 24 hours mice were treated with one of 4 different treatments including isoleucine-lysine-valine-alanine-valaine(IKVAV), IKVAVpeptide, peptide and mannitol (vehicle). Functional improvement was assessed every day using Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale. 28 days later, the mice were euthanized, and spinal cord segments were studied histologically. Statistical analysis, one-way and two-way analysis of variance (ANOVA) and linear regression model were used to measure some parameters and describe the outcome after SCI. Over a 4weeks period, IKVAV-peptide group demonstrated statistical and histological evidence of cellular reconstruction and behavioral improvement. The BBB score in the IKVAV-peptide group increased by 5.4 (25%) points, the IKVAV and peptide groups by approximately 1 point (5%) and the mannitol group by 4 points (19%). The number of protoplasmic astrocytes in the IKVAV-peptide group was significantly increased compared to IKVAV, mannitol and normal groups but not with the peptide group (p<0.001). Neuron and muscle bundle size were also increased significantly (p<0.05 and p<0.007, resp.) in the IKVAV-peptide group compared to other treatment groups. The treated control groups showed cellular and gross damages including neuron inactivation and muscle atrophy, gliosis and inability of movement. / Graduation date: 2013

No description available.

The present study examined the effects of physical disability in fathers on the development and adjustment of their children. There is little empirically based information about the influence of physical characteristics of parents on children, but speculative articles have described many deleterious effects of being raised by a physically handicapped parent. These hypothesized relations between parental disability and child adjustment were tested. Two groups of adult children selected through the Veterans Administration Spinal Cord Injury system were studied: (a) Disabled Parent (DP)--17 male and 28 female children, mean age 21.6, who were raised by a spinal cord injured father from a mean age of 1.31, and (b) Comparison (C)--15 male and 21 female children, mean age 23.8, with nondisabled fathers. The two groups were matched on father's age, education level, state of residence, and disposable family income. Children had lived with both parents until age 15, and their fathers were veterans. Subjects completed a battery of tests: the Minnesota Multiphasic Personality Inventory (MMPI), Sixteen Personality Factor Questionnaire (16PF), Bem Sex Role Inventory, Body-Cathexis scale, Parent-Child Relations Questionnaire II (PCR), and Buck-Hohmann questionnaire (designed specifically for this study). The results did not support any of the hypothesized relations between parental disability status and child adjustment. DP and C children scored within the normal range on the MMPI and 16PF. The only significant difference which emerged was that DP children tended to be more cautious in emotional expression than did C subjects. The DP and C groups did not differ in body image or sex role orientation. On the Rokeach Value Survey, DP children ranked national security, a world at peace, clean, obedient, and responsible higher than did C children. C children valued being logical more than DP children. As perceived by the children, DP and C fathers did not differ significantly in the degree to which they were loving or rejecting, casual or demanding (PCR). On the Buck-Hohmann questionnaire, there was no evidence that disabled fathers excluded themselves from discipline and childrearing aspects of parenthood or that disabled fathers lose control over their children. DP children were found to hold significantly more positive attitudes toward their fathers than were C children. There were no effects on children's health patterns or interpersonal relations as a function of the father's disability status. DP children expressed more interest and participation in athletics than did C children. It was concluded that parental disability does not pose a severe threat to child adjustment. Children with spinal cord injured fathers appeared to be well-adjusted, emotionally stable persons who highly regarded their fathers. Limitations of the study and implications for rehabilitation programs, adoption and court custody decisions, and future research were discussed.

Tyrimo problema: Juosmeninės stuburo dalies radikulopatija yra vienas iš labiausiai paplitusių sveikatos sutrikimų. Radikulopatijos metu juosmens srityje jaučiamas skausmas, mažėja stuburo paslankumas, vystosi neurologiniai sutrikimai, funkcinė negalia, pacientai tampa nedarbingi. Pakitusi sveikatos būklė – nemažai finansinių išlaidų reikalaujanti problema. Šiame darbe analizuojama, kaip kineziterapijos pratimai ir pratimai su „Red-cord” įranga veikia darbingo amžiaus žmonių nugaros skausmo intensyvumą ir funkcinę būklę. Tyrimo objektas: Skausmo ir funkcinės būklės pokyčiai taikant pratimus su „Red-cord” įranga. Tikslas: Įvertinti pratimų su „Red-cord” įranga veiksmingumą esant juosmeninės stuburo dalies radikulopatijai. Tyrimo uždaviniai: 1. Įvertinti kineziterapijos be įrangos poveikį tiriamųjų skausmo intensyvumui ir funkcinei būklei. 2. Įvertinti pratimų su „Red-cord” įranga poveikį tiriamųjų skausmo intensyvumui ir funkcinei būklei. 3. Palyginti kineziterapijos be įrangos ir pratimų su „Red-cord” įranga poveikį. Išvados: 1. Tiriamiesiems, kurie atliko kineziterapijos pratimus be įrangos, skausmo intensyvumas, nervinių šaknelių spaudimo požymis ir funkcinė negalia sumažėjo, o stuburo paslankumas ir liemens raumenų statinė ištvermė padidėjo. 2. Tiriamiesiems, kurie atliko pratimus su „Red-cord” įranga, skausmo intensyvumas, nervinių šaknelių spaudimo požymis ir funkcinė negalia sumažėjo, o stuburo paslankumas ir liemens raumenų statinė ištvermė padidėjo. 3. Pratimai su... [toliau žr. visą tekstą] / Problem of study: Radiculopathy of the lumbar spine is one of the most common illnesses. Patients with radiculopathy of lumbar spine feel pain in the lumbar area of the spine, the mobility of spine decreases, neurologic disorders are developing, patients become invalid. Back pain becomes not only health’s, but also an economical problem. In this study there will be analyzed, how common physical therapy exercises and exercises with the “Red-cord” equipment will affect back pain intensity and functional condition of working–age people. Object of study: Changes of pain and functional condition performing exercises with „Red-cord“ equipment. Aim of the study: Evaluate the effectiveness of exercises with „Red-cord” equipment for patients with spinal lumbar radiculopathy. Goals of study: 1. To assess the effect of physical therapy on pain intensity and functional condition for the patients. 2. To assess the effect of exercises with “Red-cord” equipment on pain intensity and functional condition for the patients. 3. To compare the effect of physical therapy exercises with and without “Red-cord” equipment. Conclusions: 1. For the subjects, who performed physiotherapy without equipment, pain intensity, neurological symptoms and negative effect on every day activity significantly decreased, and spine mobility together with muscle static endurance significantly increased. 2. For the subjects, who performed exercises on “Red-cord” equipment, pain intensity, neurological symptoms... [to full text]

The first part of my thesis involves an investigation into mechanisms underlying the presynaptic regulation of transmitter release from myelinated hindlimb sensory afferents in rodents. The central hypothesis is that in addition to chemical transmission in spinal neuronal networks, electrical synapses formed by connexins are critically involved in presynaptic inhibition of large diameter sensory afferents. Subsequent sections of the thesis present a detailed examination of the distribution of connexins in the rodent spinal cord with a particular emphasis on the neuronal connexin, Cx36. Connexin36 (Cx36) is widely believed to be the protein forming the neuronal gap junctions that create electrical synapses between mammalian neurons in many areas of the central nervous system (Condorelli et al 1998). The first part of thesis concerns a previously unknown role of neuronal connexins in interneurone pathways involved in presynaptic control of synaptic transmission in the lumbar spinal cord of rodents. As far as we are aware, the idea that electrical contacts between spinal neurons contribute to spinal presynaptic inhibition is a novel hypothesis. Evidence will be presented: 1) that Cx36 is present in regions of the spinal cord containing interneurons involved in presynaptic inhibition, 2) that the lack of Cx36 in Cx36-/- knockouts mice results in a severe impairment of presynaptic inhibition, and 3) that blocking gap junctions pharmacologically in wild type mice impairs presynaptic inhibition. The exploration of this hypothesis will involve a combination of electrophysiological and immunohistochemical approaches in juvenile wild-type and knockout mice lacking Cx36, as well as immunohistochemical observations in adult rodents. This first section of the thesis begins with the development of a preparation in which several measures of presynaptic inhibition described in the in vivo adult cat preparation can be examined in vitro in young mice. The following sections of the thesis describe the distribution and features of Cx36 on neurons in mice and rats of different ages in four parts. The first will show that Cx36 is the only connexin associated with spinal neurons and refutes claims in the literature about the existence of a variety of connexions on spinal neurons. The second part will show that while gap junctions between some spinal neurons are only a transient developmental phenomenon, they persist in abundance in adult animals. The third part will present evidence of a previously unsuspected III association of Cx36 gap junctions at the chemical synapse between muscle afferent fibres and motoneurons. Specifically, an association between Cx36 and the glutamate transporter used in primary afferents, Vglut1 will be described. To our knowledge these results are the first to suggest the existence of mixed (electrical and chemical) synapses between primary afferents and motoneurons in the mature mammalian spinal cord. The final part of the thesis will describe the presence of Cx36 gap junctions on adult sacral motoneurons involved in control of sexual, urinary and defecation functions in the rodent.

The first part of my thesis involves an investigation into mechanisms underlying the presynaptic regulation of transmitter release from myelinated hindlimb sensory afferents in rodents. The central hypothesis is that in addition to chemical transmission in spinal neuronal networks, electrical synapses formed by connexins are critically involved in presynaptic inhibition of large diameter sensory afferents. Subsequent sections of the thesis present a detailed examination of the distribution of connexins in the rodent spinal cord with a particular emphasis on the neuronal connexin, Cx36. Connexin36 (Cx36) is widely believed to be the protein forming the neuronal gap junctions that create electrical synapses between mammalian neurons in many areas of the central nervous system (Condorelli et al 1998). The first part of thesis concerns a previously unknown role of neuronal connexins in interneurone pathways involved in presynaptic control of synaptic transmission in the lumbar spinal cord of rodents. As far as we are aware, the idea that electrical contacts between spinal neurones contribute to spinal presynaptic inhibition is a novel hypothesis. Evidence will be presented: 1) that Cx36 is present in regions of the spinal cord containing interneurones involved in presynaptic inhibition, 2) that the lack of Cx36 in Cx36-/- knockouts mice results in a severe impairment of presynaptic inhibition, and 3) that blocking gap junctions pharmacologically in wild type mice impairs presynaptic inhibition. The exploration of this hypothesis will involve a combination of electrophysiological and immunohistochemical approaches in juvenile wild-type and knockout mice lacking Cx36, as well as immunohistochemical observations in adult rodents. This first section of the thesis begins with the development of a preparation in which several measures of presynaptic inhibition described in the in vivo adult cat preparation can be examined in vitro in young mice. The following sections of the thesis describe the distribution and features of Cx36 on neurones in mice and rats of different ages in four parts. The first will show that Cx36 is the only connexin associated with spinal neurons and refutes claims in the literature about the existence of a variety of connexions on spinal neurons. The second part will show that while gap junctions between some spinal neurons are only a transient developmental phenomenon, they persist in abundance in adult animals. The third part will present evidence of a previously unsuspected III association of Cx36 gap junctions at the chemical synapse between muscle afferent fibres and motoneurones. Specifically, an association between Cx36 and the glutamate transporter used in primary afferents, Vglut1 will be described. To our knowledge these results are the first to suggest the existence of mixed (electrical and chemical) synapses between primary afferents and motoneurones in the mature mammalian spinal cord. The final part of the thesis will describe the presence of Cx36 gap junctions on adult sacral motoneurones involved in control of sexual, urinary and defecation functions in the rodent.

Biochemical assays and radioabsorptiometry evaluated the relationship of mineral and bone metabolism to the systemic response to neurotrauma or orthopaedic trauma of adult males. Forty-one adult males (29.4±9.3 years) participated of which 37 had a primary diagnosis of traumatic spinal cord injury (SCI) and four were vertebral fracture controls. Biochemical abnormalities found included hyperphosphataemia, in association with low or low normal serum levels of 1,25-dihydroxyvitmain D (1,25(OH)₂D) and of parathyroid hormone (PTH), whilst patients remained normocalcaemic. These disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone were strongly associated with the interval since injury and the severity of injury, but none of these relationships was correlated with the level of the injury, the sensory status of a patient or the presence of spine fracture. The disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone found in this study are a mirror image of the data of patients with the heritable disorders autosomal dominant hyperphosphataemic rickets (ADHR), which results from an inactivating mutation of the gene encoding fibroblast growth factor 23 (FGF23) and autosomal recessive hypophosphataemic rickets (ARHR), which is caused by a mutation of the gene encoding dentin matrix protein-1 (DMP-1). It is potentially important that the hormone/proteolytic enzyme/extra-cellular matrix protein cascade associated with these disorders is counter-regulated by 1,25(OH)₂D, acting either directly or indirectly. The present results suggest that the serum levels of 1,25(OH)₂D of the neurotrauma patients chosen for study may have been inappropriately high with respect to the “physiological and metabolic set” of serum levels of phosphate and ionised calcium in the period corresponding to the uncoupling of the resorption and formation of bone, at least in males, prompting further investigation. The findings are consistent with a new “physiological set,” possibly involving an abnormality in the synthesis or processing of the endocrine fibroblast growth factors or other circulating phosphatonins, which may act as an additional level of regulation of the renal–bone axis, rather than renal failure. Strongly supporting this was the dynamic pattern of the biochemistry and radiological data of these neurotrauma patients and also, preliminary evidence of disturbances in circulating levels of other systemic modulators of mineral and bone metabolism. The relationships that were observed potentially may be explained by the diversity of the physiological activities of the endocrine fibroblast growth factors and the modes of actions of secreted FGF23 in bone. The findings provide an understanding of why bone loss occurs and may form the target for safe and cost effective interventions. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1345019 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, Discipline of Orthopaedics and Trauma, 2008

Biochemical assays and radioabsorptiometry evaluated the relationship of mineral and bone metabolism to the systemic response to neurotrauma or orthopaedic trauma of adult males. Forty-one adult males (29.4±9.3 years) participated of which 37 had a primary diagnosis of traumatic spinal cord injury (SCI) and four were vertebral fracture controls. Biochemical abnormalities found included hyperphosphataemia, in association with low or low normal serum levels of 1,25-dihydroxyvitmain D (1,25(OH)₂D) and of parathyroid hormone (PTH), whilst patients remained normocalcaemic. These disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone were strongly associated with the interval since injury and the severity of injury, but none of these relationships was correlated with the level of the injury, the sensory status of a patient or the presence of spine fracture. The disturbances of phosphate and vitamin D metabolism and the markedly accelerated resorption of bone found in this study are a mirror image of the data of patients with the heritable disorders autosomal dominant hyperphosphataemic rickets (ADHR), which results from an inactivating mutation of the gene encoding fibroblast growth factor 23 (FGF23) and autosomal recessive hypophosphataemic rickets (ARHR), which is caused by a mutation of the gene encoding dentin matrix protein-1 (DMP-1). It is potentially important that the hormone/proteolytic enzyme/extra-cellular matrix protein cascade associated with these disorders is counter-regulated by 1,25(OH)₂D, acting either directly or indirectly. The present results suggest that the serum levels of 1,25(OH)₂D of the neurotrauma patients chosen for study may have been inappropriately high with respect to the “physiological and metabolic set” of serum levels of phosphate and ionised calcium in the period corresponding to the uncoupling of the resorption and formation of bone, at least in males, prompting further investigation. The findings are consistent with a new “physiological set,” possibly involving an abnormality in the synthesis or processing of the endocrine fibroblast growth factors or other circulating phosphatonins, which may act as an additional level of regulation of the renal–bone axis, rather than renal failure. Strongly supporting this was the dynamic pattern of the biochemistry and radiological data of these neurotrauma patients and also, preliminary evidence of disturbances in circulating levels of other systemic modulators of mineral and bone metabolism. The relationships that were observed potentially may be explained by the diversity of the physiological activities of the endocrine fibroblast growth factors and the modes of actions of secreted FGF23 in bone. The findings provide an understanding of why bone loss occurs and may form the target for safe and cost effective interventions. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1345019 / Thesis (Ph.D.) - University of Adelaide, School of Medicine, Discipline of Orthopaedics and Trauma, 2008