%0 Journal Article
%~ Pubmed
%A Moalem-Taylor, Gila
%A Li, Man
%A Allbutt, Haydn N
%A Wu, Ann
%A Tracey, David J
%T A preconditioning nerve lesion inhibits mechanical pain hypersensitivity following subsequent neuropathic injury.
%B 
%D 2011
%V 7
%N 
%P 1
%@ 1744-8069
%X A preconditioning stimulus can trigger a neuroprotective phenotype in the nervous system - a preconditioning nerve lesion causes a significant increase in axonal regeneration, and cerebral preconditioning protects against subsequent ischemia. We hypothesized that a preconditioning nerve lesion induces gene/protein modifications, neuronal changes, and immune activation that may affect pain sensation following subsequent nerve injury. We examined whether a preconditioning lesion affects neuropathic pain and neuroinflammation after peripheral nerve injury.
%Z FOR Codes: 110905



%0 Journal Article
%A Slack, K
%A Billing, Robyn
%A Matthews, Slade
%A Allbutt, Haydn
%A Einstein, Rosemarie
%A Henderson, Jasmine
%T Subtle Cardiovascular Dysfunction in the Unilateral 6-Hydroxydopamine-Lesioned Rat
%B Parkinson''s Disease
%D 2010
%C United States
%I Sage - Hindawi Access to Research
%V 2010
%N 
%P 427810
%@ 2042-0080
%X 
%Z FOR Codes: 110201



%0 Journal Article
%~ Pubmed
%A Warraich, S T
%A Allbutt, H N
%A Billing, R
%A Radford, J
%A Coster, M J
%A Kassiou, M
%A Henderson, J M
%T Evaluation of behavioural effects of a selective NMDA NR1A/2B receptor antagonist in the unilateral 6-OHDA lesion rat model.
%B Brain research bulletin
%D 2009
%V 78
%N 2-3
%P 85-90
%@ 1873-2747
%X The degeneration of the dopaminergic nigrostriatal pathway in Parkinson's disease (PD) is associated with altered transmission at striatal NMDA receptors containing NR2B subunits. We investigated a potential novel therapeutic compound, 4-trifluoromethoxy-N-(2-trifluoromethyl-benzyl)-benzamidine (BZAD-01), a selective NMDA NR1A/2B receptor antagonist for PD and compared it with levodopa, the standard treatment for PD. This study also evaluated whether combining levodopa and BZAD-01 gave better improvements of parkinsonian symptoms. Parkinsonism was induced by microinjection of the toxin, 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) of 40 Sprague-Dawley rats. Parkinsonism and the efficacy of drugs were assessed using a battery of behavioural tests including balance beam, apomorphine-induced rotation, body axis bias or "curling", head position bias and disengage sensorimotor latency test. Immunohistochemistry was performed on post-mortem tissue to estimate the loss of dopaminergic neurons. The main effects were that BZAD-01 co-administration prevented chronic levodopa-induced potentiation of apomorphine rotation. However levodopa-treated rats were slower than either controls or BZAD-01-treated rats in the locomotor test. The improvement in the apomorphine rotation test suggests that BZAD-01 may be a useful adjunct to levodopa monotherapy.
%Z FOR Codes: 110903



%0 Journal Article
%~ Pubmed
%A Truong, L
%A Allbutt, H N
%A Coster, M J
%A Kassiou, M
%A Henderson, J M
%T Behavioural effects of a selective NMDA NR1A/2B receptor antagonist in rats with unilateral 6-OHDA+parafascicular lesions.
%B Brain research bulletin
%D 2009
%V 78
%N 2-3
%P 91-6
%@ 1873-2747
%X Experimental lesions involving the parafascicular (Pf) nucleus and medial forebrain bundle (MFB) may model to some extent the pathological loss of glutamatergic neurons from the centromedian-parafascicular (CM-Pf) complex and nigral dopaminergic cell loss observed clinically at post-mortem in Parkinson's disease (PD) cases. Our study investigated whether there were alterations in symptomatology in such rats with unilateral 6-OHDA+Pf lesions after treatment with either a selective NR1A/NR2B NMDA antagonist and/or l-dopa. Rats were given dual surgery to the MFB with 6-hydroxydopamine (6-OHDA) and Pf with N-methyl-d-aspartate (NMDA). (i) An NR1A/NR2B selective NMDA antagonist (BZAD-01; 10mg/kg), (ii) l-dopa (25mg/kg), (iii) BZAD-01+l-dopa (10mg/kg; 25mg/kg) or (iv) vehicle solution were administered for 6 weeks, during which behavioural testing was performed. BZAD-01 improved postural asymmetry in the first month as well as apomorphine-induced rotation. The latter was also improved by l-dopa in this model. These data support the use of selective NR1/NR2B NMDA antagonists in the therapeutics of PD.
%Z FOR Codes: 110904



%0 Journal Article
%~ Pubmed
%A Leaver, Katherine R
%A Allbutt, Haydn N
%A Creber, Nathan J
%A Kassiou, Michael
%A Henderson, Jasmine M
%T Oral pre-treatment with epigallocatechin gallate in 6-OHDA lesioned rats produces subtle symptomatic relief but not neuroprotection.
%B Brain research bulletin
%D 2009
%V 80
%N 6
%P 397-402
%@ 1873-2747
%X Much recent work is investigating the role of oxidative stress and inflammatory mechanisms in the aetiology of neurodegeneration in Parkinson's disease. The present study evaluated whether the green tea constituent epigallocatechin gallate (EGCG) which has both anti-oxidant and anti-inflammatory properties, exerts neuroprotection and symptomatic effects when administered orally as a pre-treatment prior to 6-hydroxydopamine (6-OHDA) lesions. Groups of rats were given either 1mg/kg, 2mg/kg EGCG or vehicle solution for 14 days. Sham or 6-OHDA surgery was performed on day 11 of the drug administration protocol. Behavioural analysis was conducted before drugs/vehicle solution, again during the treatment period and then repeated at fortnightly intervals for 2 months post-operatively. Whilst some subtle behavioural improvements in postural abnormalities and ability to cross a narrow beam were observed in lesioned rats after EGCG (vs. vehicle) there was no evidence of neuroprotection on post-mortem quantification of degree of nigral dopaminergic neuronal loss when comparing the lesioned groups given the various treatments.
%Z FOR Codes: 110903



%0 Journal Article
%~ Pubmed
%A van Dijk, Addy
%A Johnston, Christopher
%A Allbutt, Haydn
%A Kassiou, Michael
%A Henderson, Jasmine
%T Behavioural effects of trishomocubanes in rats with unilateral 6-hydroxydopamine lesions.
%B Behavioural Brain Research
%D 2008
%V 190
%N 1
%P 14-21
%@ 0166-4328
%X Whilst dopamine replacement improves cardinal features of Parkinson's disease, chronic levodopa administration is associated with dose-related side effects and not all symptoms are ameliorated, necessitating the development of new treatments. Studies of trishomocubanes, a novel group of sigma ligands, have shown enhanced amphetamine-stimulated striatal release of dopamine and a potentially neuroprotective action in vitro and reversal of reserpine-induced catalepsy in vivo. Such effects warrant investigation in animal models of parkinsonism. Our study therefore examines two novel trishomocubane compounds, N-(3'-fluorophenyl)methyl-4-azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ol (1) and, N-(3'-fluorophenyl)ethyl-4-azahexacyclo[5.4.1.0(2,6).0(3,10).0(5,9).0(8,11)]dodecan-3-ol (2) in the 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease. A variety of motor behaviours were studied in rats given 6-OHDA lesions. Groups of lesioned rats were given either (1) or (2) or vehicle solution i.p. Acute administration of 3mg/kg (1) resulted in a decrease in locomotor activity. Twenty-five milligrams per kilogram (2) caused a decrease in locomotor activity at t=10 and t=20 min of the locomotor test but this was not found when (2) was co-administered with either apomorphine or amphetamine. The decreased locomotor activity indicates that (1) and (2) may have sedative/anxiolytic effect(s). However, elevated plus maze data failed to demonstrate anxiolysis with (2). Quantification of dopaminergic neurons did not demonstrate any significant difference in the magnitude of cell loss between drug-treated vs. vehicle treated rats so no neuroprotective effect was demonstrated in this model at the doses utilised.
%Z FOR Codes: 110903



%0 Journal Article
%~ Pubmed
%A Leaver, Kr
%A Allbutt, Hn
%A Creber, Nj
%A Kassiou, M
%A Henderson, Jm
%T Neuroprotective effects of a selective N-methyl-D-aspartate NR2B receptor antagonist in the 6-hydroxydopamine rat model of Parkinson's disease.
%B Clinical and Experimental Pharmacology & Physiology
%D 2008
%V 35
%N 11
%P 1388-94
%@ 1440-1681
%X 1. Current pharmacotherapies for the treatment of Parkinson's disease (PD) are largely symptomatic and do not attenuate the characteristic nigral (dopamine) cell loss. 2. Using the 6-hydroxydopamine (6-OHDA) rat model of PD, we investigated the novel, potentially neuroprotective compound BZAD-01, which is an N-methyl-D-aspartate (NMDA) glutamate receptor antagonist selective for the NR2B subunit. 3. Forty female Sprague-Dawley rats were pretreated with either 10 mg/kg BZAD-01 or vehicle (5% sucrose and 0.1% ascorbate) in their drinking water for 11 days prior to and for 3 days following 6-OHDA surgery. During surgery, rats received an injection of either a toxic dose of 16 microg 6-OHDA or a non-toxic dose of 1 microg 6-OHDA (sham) into the medial forebrain bundle. A series of behavioural tests, including curling (measuring body axis bias), head position bias and narrow beam, was performed fortnightly for 8 weeks after surgery to assess the effects of BZAD-01 pretreatment on parkinsonism. Drug-induced rotational asymmetry was also assessed just before rats were killed. Post-mortem immunohistochemistry was performed to quantify the degree of nigral dopamine cell loss. 4. Pretreatment of 6-OHDA-lesioned rats with BZAD-01 significantly reduced the amount of dopamine cell loss and significantly improved all behavioural measures. Furthermore, there was no significant difference in any of the behavioural measures between lesioned rats pretreated with BZAD-01 and rats that underwent sham surgery.
%Z FOR Codes: 110313 110904



%0 Journal Article
%~ Pubmed
%A Oehrn, Carina
%A Allbutt, Haydn
%A Henderson, Jasmine
%T Effect of ventrolateral thalamic nucleus lesions in the unilateral 6-hydroxydopamine rat model.
%B Behavioural Brain Research
%D 2007
%V 183
%N 1
%P 67-77
%@ 0166-4328
%X Whilst dysfunction of basal ganglia-thalamic circuitry is implicated in the genesis of parkinsonian symptomatology, few studies have examined the effects of lesioning the motor thalamus in the context of parkinsonism. Forty rats were therefore subdivided into four lesion groups each of 10 rats with lesions or sham surgery targeting (1) the medial forebrain bundle and/or (2) motor thalamus, resulting in: Sham/Sham, 6-OHDA/Sham, Sham/NMDA and 6-OHDA/NMDA groups. Behavioural testing was performed prior to any surgery and after each surgery including analysis of posture, drug-induced rotation, sensorimotor and autonomic deficits. As expected 6-OHDA lesions induced abnormalities in posture, locomotion, sensorimotor and pilomotor function, ipsilateral and contralateral rotational asymmetries after amphetamine and apomorphine, respectively. These behavioural changes reflect parkinsonism in this model. Additional thalamic lesions virtually abolished apomorphine-induced rotational asymmetry and improved sensorimotor response latency to tactile stimulation on the contralateral side. These data support the contribution of dysfunctional motor thalamic circuitry in rotational asymmetry and abnormal sensorimotor function in parkinsonian rats.
%Z FOR Codes: 110903



%0 Journal Article
%~ Pubmed
%A Allbutt, Haydn N
%A Siddall, Phillip J
%A Keay, Kevin A
%T Contusive spinal cord injury evokes localized changes in NADPH-d activity but extensive changes in Fos-like immunoreactivity in the rat.
%B Journal of anatomy
%D 2007
%V 211
%N 3
%P 352-70
%@ 0021-8782
%X The histological detection of nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), a marker for nitric oxide-producing cells, was used to evaluate ongoing changes in the neural biochemistry of the rat spinal cord 1 week following contusive spinal cord injury (SCI). In addition, the immunohistochemical detection of the immediate-early gene c-fos was used to identify basal patterns of neural activity at this time. The numbers and laminar locations of NADPH-d- and c-fos-positive cells were examined in spinal segments adjacent to the site of injury (T12-S3) as well as those distant from the injury (C3-C5) in both SCI and un-injured rats. Our data show that contusive SCI results in a significant reduction in NADPH-d labelling in the superficial dorsal horn, and a significant increase in NADPH-d expression in small bipolar neurons and large motoneurons in the ventral horn at the site of the injury. In spinal segments distant to the injury site (C3-C5), NADPH-d activity did not differ from that of uninjured controls. Furthermore, significant reductions in the levels of c-fos expression were observed in SCI rats, in spinal segments both at and distant to the site of injury for all spinal laminae. The only exception was a dramatic increase observed in the sacral parasympathetic nucleus. These data suggest that increased NADPH-d expression is related to conditions specific to the site of injury, whereas the changes in c-fos expression probably indicate more global changes in neuronal activity following SCI.
%Z FOR Codes: 110903



%0 Journal Article
%~ Pubmed
%A Allbutt, Haydn N
%A Henderson, Jasmine M
%T Use of the narrow beam test in the rat, 6-hydroxydopamine model of Parkinson's disease.
%B Journal of Neuroscience Methods
%D 2006
%V 159
%N 2
%P 195-202
%@ 0165-0270
%X Batteries of behavioural tests provide a method by which researchers may examine specific functional pathways. The narrow beam test examines the ability of a rat to cross a narrow, elevated beam of wood or other material. In order to determine the utility of the narrow beam test in the study of Parkinsonism, it was of interest to characterise the performance of animals at this task. Rats were placed at one end of a 105 cm long, elevated beam and both the time it took to begin crossing the beam, as well as the total time taken to cross the beam, were measured. The effects of training, time of day and 6-hydroxydopamine lesion on beam performance were examined. Rats reached maximal performance at the task within a single test session and time of day had no effect on beam performance. Parkinsonian rats demonstrated a four-fold increase in both the latency to initiate the task and the total time to cross the beam (p < 0.05).
%Z FOR Codes: 110904



%0 Journal Article
%~ Pubmed
%A Truong, L
%A Allbutt, H
%A Kassiou, M
%A Henderson, J M
%T Developing a preclinical model of Parkinson's disease: a study of behaviour in rats with graded 6-OHDA lesions.
%B Behavioural Brain Research
%D 2006
%V 169
%N 1
%P 1-9
%@ 0166-4328
%X Injection of increasing concentrations of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) can be used to establish a graded model of different clinical stages of Parkinson's disease (PD). We investigated the relationship between behavioural alterations and loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Forty female Sprague-Dawley rats were injected with either (i) 4 microg (ii) 8 microg or (iii) 16 microg 6-hydroxydopamine (6-OHDA) to mimic the preclinical, mild and advanced clinical stages of PD, respectively. Vehicle was injected in a separate control group. Behaviours analysed included postural asymmetry, balance, locomotion, sensorimotor deficits and apomorphine rotation. At post-mortem the degree of tyrosine immunoreactive dopaminergic cell (TH-ir) loss was then estimated. There was a graded and consistent trend in each of the behaviours studied with respect to cell loss between the different sized lesion groups when examined using correlation analysis (all comparisons, r > 0.8, p < 0.001). Rats with large lesions demonstrated more significant behavioural changes over 8 weeks of testing than those with intermediate and smaller lesions (group comparisons p < 0.001). PD symptomatology became overt when cell loss reached 70%, however some significant changes can be observed with as little as 40% dopaminergic cell loss. Thus, injection with increasing concentrations 6-OHDA into the MFB can produce increasing extents of cell loss and behavioural changes, which were well correlated. This graded model can be useful for testing potential neuroprotective compounds for PD.
%Z FOR Codes: 110903



%0 Journal Article
%~ Pubmed
%A Henderson, Jasmine
%A Doherty, Kristy
%A Allbutt, Haydn
%A Billing, Robyn
%T Effects of pallidotomy on motor symptoms in an animal model of Parkinson's disease.
%B Behavioural Brain Research
%D 2006
%V 169
%N 1
%P 29-38
%@ 0166-4328
%X The present study was designed to evaluate the motor effects of lesioning the internal globus pallidus in an animal model of Parkinson's disease. Fourty rats were divided into four groups (each of 10 rats) which received either unilateral 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle (mfb) plus sham surgery to the pallidum, sham surgery of mfb plus N-methyl-D-aspartate (NMDA) induced pallidal lesions, combined 6-OHDA mfb + NMDA pallidal lesions or sham surgery to both structures. Animals with 6-OHDA lesions developed significant ipsilateral biases in head position, body axis and circling after amphetamine challenge (all P < 0.05). Prominent contralateral deficits were present in sensorimotor response latency and contralateral circling was induced by apomorphine challenge (both P < 0.05). The addition of an NMDA pallidal lesion, improved the head position and body axis biases, as well as dopamine-agonist induced rotation and contralateral reaction time in a sensorimotor task (all P < 0.05). There was, however, a slight worsening of sensorimotor response on the ipsilateral side (P < 0.05). Pallidal lesions in the absence of 6-OHDA lesions produced contralateral head position and body axis biases (both P < 0.05). These data indicate that pallidotomy improves some, but not all aspects of parkinsonian motor dysfunction in an animal model of Parkinson's disease (PD).
%Z FOR Codes: 110502



%0 Journal Article
%~ Pubmed
%A Henderson, J M
%A Schleimer, S B
%A Allbutt, H
%A Dabholkar, V
%A Abela, D
%A Jovic, J
%A Quinlivan, M
%T Behavioural effects of parafascicular thalamic lesions in an animal model of parkinsonism.
%B Behavioural Brain Research
%D 2005
%V 162
%N 2
%P 222-32
%@ 0166-4328
%X We recently reported that the centromedian-parafascicular thalamic complex (CM-Pf) degenerates in Parkinson's disease and progressive supranuclear palsy. The contribution of such thalamic pathology to disease symptoms has not yet been established. The present study therefore investigated the behavioural impact of lesioning the corresponding thalamic region (termed Pf) on a range of behaviours present in rodents. There were four surgical groups: (1) sham medial forebrain bundle (mfb)+sham Pf, (2) 6-OHDA mfb lesion+sham Pf, (3) sham mfb+NMDA Pf lesion, (4) 6-OHDA+NMDA Pf lesions. Posture, sensory functions and apomorphine-induced rotational asymmetry were assessed before and after each surgery. Other assessments performed including a timed motivational task, grooming behaviours and piloerection. 6-OHDA lesions induced postural (ipsilateral curling and head position biases), sensorimotor (increased latency to respond to tactile stimulation of the contralateral side when eating or grooming) and rotational abnormalities (contralateral circling after apomorphine). The main effects of combined 6-OHDA+Pf lesions were improved performance in a motivational task (decreased latency to retrieve reward) but worsened piloerection, relative to animals with either 6-OHDA or Pf lesions alone. The thalamic zone common to all lesioned animals involved the posterior Pf. Our data suggests that the posterior CM-Pf may be involved in motivational responses and autonomic dysfunction in parkinsonian disorders.
%Z FOR Codes: 110903