The motor cortex makes a substantial contribution to contralateral limb functionvia the corticospinal tract (CST). The extent to which the motor cortexinfluences ipsilateral limb function is less clear. Interest in ipsilateral corticalcontrol stems from studies of stroke survivors, demonstrating increasedactivation of the ipsilateral motor cortex during movement of the affected limb.This raises the possibility that ipsilateral pathways contribute to recovery offunction following damage to the contralateral CST. The overarching aim of thisthesis was to extend the knowledge of neural systems that might mediateipsilateral actions of the motor cortex, both under normal circumstances andafter stroke.In rodent models of stroke, there is evidence that CST axons originating from thenon-ischaemic hemisphere sprout into the denervated (ipsilateral) side of thespinal cord, and the extent of sprouting correlates with the degree of motorrecovery. However, it is yet to be confirmed whether the CST from the nonischaemichemisphere establishes new terminals in the denervated (ipsilateral)side of the spinal cord to replace connections lost after stroke. Hence, the firstmajor aim of this thesis was to assess for CST terminal remodelling between thenon-ischaemic hemisphere and the denervated (ipsilateral) side of the cervicalspinal cord following recovery from experimental stroke in the rat. Ratsunderwent 60 min middle cerebral artery occlusion (MCAo) or sham occlusionsurgery. Behavioural testing was conducted prior to MCAo and postoperativelyfor 28 days to monitor functional deficit and recovery. At day 28, theanterograde tracer cholera toxin b (CTb) subunit was injected into the forelimbmotor cortex of the non-ischaemic hemisphere. Spinal sections containinganterogradely labelled terminals were reacted with antibodies against CTb andimmunoreactive terminals were quantified. MCAo was associated with loss ofapproximately 35% of CST axons originating from the ischaemic hemisphere andinfarcts were localised to subcortical structures. Rats exhibited sensorimotordeficits in the early phase after MCAo but recovered over time such that therewere no significant differences in sensorimotor performances between shamoperatedand MCAo rats at post-operative day 28. Despite functional recoverydemonstrated by MCAo rats, the number of CTb-labelled terminals in theIIcervical spinal cord originating from the non-ischaemic hemisphere was notaltered compared to shams. The results of this first study suggest that aftersubcortical stroke, the motor cortex from the non-ischaemic hemisphere doesnot contribute to recovery of the affected limb via increasing its direct CSTconnections to the denervated (ipsilateral) side of the spinal cord. If the motorcortex from the non-ischaemic hemisphere does take over control of ipsilateralspinal circuitry after stroke, it likely utilises an indirect route.In the intact animal, a number of indirect routes via which the motor cortex maygain access to ipsilateral spinal circuitry have been identified. These pathwaysare complex and involve intercalated neurons located in the brainstem andcontralateral spinal cord. However, there are numerous putative indirect routeswhich have yet to be investigated. One such route involves contralaterallydescending CST axons targeting spinal commissural interneurons (CINs), which inturn would either mono- or polysynaptically affect motor neurons on theopposite side of the spinal cord. CINs are a heterogeneous population of cellsimportant for inter-limb coordination. Despite the importance of CINs tolocomotion and their potential role in providing the motor cortex indirect accessto ipsilateral spinal circuits, supraspinal input to CINs is poorly defined. Hence,the second major aim of this thesis was to characterise contacts to CINs fromdifferent supraspinal sources (the CST and reticulospinal tract (ReST)) in thecervical spinal cord of the intact rat. The CINs included i) those that issue longrangeaxonal projections to lumbar segments, termed long-descendingpropriospinal neurons (LDPNs), and ii) those that issue short-range axonalprojections confined to a single segment, termed intrasegmental CINs. Axonswere labelled anterogradely by injecting CTb into the forelimb motor cortex ormedial longitudinal fasciculus (MLF), to label CST and ReST axons, respectively.Fluorogold (FG) was injected unilaterally into segments L1/L2 or C3/C4 in orderto retrogradely label LDPNs or intrasegmental CINs, respectively. Spinal sectionscontaining labelled cells and terminals were immunoreacted with variousantibody combinations and were then examined with confocal microscopy. BothLDPNs and intrasegmental CINs received very few contacts from CST terminalsbut had significant numbers of contacts from ReST terminals. Use of vesicularglutamate and vesicular GABA transporters revealed that both cell typesreceived approximately 80% of excitatory and 20% of inhibitory ReST contacts.IIIThe results suggest that in the intact animal, the CST has a minimal directinfluence on LDPNs and intrasegmental CINs but the ReST has a powerful directinfluence. Therefore, following loss of CST axons (e.g. after stroke), the corticoreticulospinal-commissural pathway has the capacity to deliver information fromthe intact hemisphere to the denervated side of the spinal cord.
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