Studies of motor cortex plasticity after stroke have revealed that both recovery and compensation can be observed at a neurophysiological level. Within the motor cortex this can be demonstrated through the expansion of movement representations within areas outside the original motor map. Motor mapping of forelimb movement representations within rat motor cortex before and after stroke.
Thomas Carmichael
Synchronous neuronal activity is a signal for axonal sprouting after cortical lesions in adults. J Neurosci. Degenerating neurons (fluoro-jade B-labeled) in the area of an ischemic lesion of the sensorimotor cortex (B,C). Synapse replacement in the striatum of the adult rat after unilateral cortex ablation. J Comp Neurol.
Campbell Teskey & Bryan Kolb
Whether cortical neurogenesis can be induced in the cortex remains a controversial question (see also Chapter 24). Environmental enrichment changes the organizational features of forelimb representation in the primary somatocortex of adult rats. Exp Brain Res. Daily effects of an enriched environment on immediate early gene expression in the rat brain.Brain Res.
Resting-state fMRI can identify temporal correlations of low-frequency BOLD signal fluctuations (<0.1 Hz) between different brain regions, indicative of functional connectivity. Ischemic damage to brain tissue can be identified with T2 and diffusion-weighted MRI, established imaging methods for the detection of stroke lesions in the clinic and laboratory. However, in recent years, MRI methods such as diffusion tensor imaging (DTI) and manganese-enhanced MRI (MEMRI) have been successfully applied to investigate neuroanatomical reorganization after stroke.
DTI enables the evaluation of three-dimensional tissue water displacement, characterized mathematically by an effective diffusion tensor composed of nine matrix elements [30]. Briefly, the diffusion tensor can be estimated by MRI with diffusion weighting gradients in multiple directions. Computational diagonalization of the diffusion tensor yields three principal orthogonal diffusivities (eigenvalues) and its three principal coordinate directions (eigenvectors), which can be used to compute scalar indices such as
The spatial characteristics of water diffusion in brain tissue are affected by anatomical barriers such as cell membranes and myelinated fibers. Calculations of diffusion anisotropy and the primary diffusion direction can be used to model fiber architecture in the human or animal brain, visualized by orientation-based color-coded FA maps or three-dimensional fiber tractography images (see Figure 6.3) [32]. Studies longitudinally performing DTI in patients and animal models have reported elevated FA and reduced mean diffusivity acutely after stroke, pointing to cytotoxic edema along with increased tortuosity of the swollen tissue, chronically followed by an increase in mean diffusivity and a decrease in FA , which was particularly prominent in affected white matter [33,34].
The manganese-induced increase in longitudinal relaxation rate, R1(1/T1), is proportional to the local manganese concentration [39], thus the amount of manganese accumulation after injection can be estimated from the difference between pre- and post-contrast R1(AR1) .
MEMRI-based neuronal tract tracing in rat brain
Leigh Leasure, Andreas Luft & Timothy Schallert
Damage to the forelimb representation area of the rat sensorimotor cortex (FL-SMC) causes deficits in limb use in the contralateral forelimb [5,6,8]. Similarly, overuse of the forelimb affected by a unilateral cortical lesion increases reactive astrocytic response in surviving perilesional tissue [10] but limits use-dependent dendritic events in the homotopic cortex [6]. We found that forced overuse of the affected limb during the first but not the second week after a lesion caused use-dependent exaggeration of the injury [19].
These could take full advantage of the brain's ability to undergo beneficial plastic changes, which is likely greater in the acute phase than in the later phases after stroke [25]. For example, dendritic arborization occurs in the homotopic region after unilateral electrolytic [5,6] but not aspiration lesions [8] of the rat sensorimotor cortex. So if one of the medications being taken (or a combination thereof) interacts with a potential stroke therapy, this interference would only be seen in clinical trials [69].
Expression of molecules related to neuronal plasticity in the striatum after aspiration and thermocoagulation lesions of the cerebral cortex in adult rats. J Neurosci. Motor and somatosensory disorders following unilateral and bilateral lesions of the cortex induced by aspiration or thermocoagulation in the adult rat. Exp Neurol. For example, typically, infarcts in the territory of the posterior cerebral artery are embolic in origin and occupy the entire supply area of the affected artery [51].
Thus, an arterial obstruction in the MCA may have different consequences for the neurological deficit and infarct manifestation, depending on the location of the occlusion [53].
In fact, a 6-second perfusion delay relative to the unaffected hemisphere before the start of stroke treatment predicted T2 lesion volume on day 8, regardless of treatment regimen. In contrast, neither the magnitude of pretreatment DWI abnormalities nor the magnitude of the apparent diffusion coefficient were predictive or discriminative. Furthermore, it became clear that the abnormalities indicated by perfusion imaging before the start of treatment were greater in patients without recanalization than in patients with successful recanalization after thrombolysis [43].
Importantly, survival of brain regions in low perfusion brain areas can influence subsequent functional reorganization [48]. Taken together, the new recanalization strategies in the treatment of acute strokes have improved the prognosis of ischemic stroke for many patients and opened new windows for understanding the impact of focal ischemia on the resulting neurological deficit and the prospects for recovery after stroke. In particular, the residual stroke lesion and associated physiological changes deserve attention because they are critical for stroke recovery.
It is well known that a stroke can affect any of the cerebral arteries, causing different neurological deficit patterns that result from the affected brain areas. In contrast, anterior cerebral artery infarcts are usually of atherosclerotic origin and more variable in lesion pattern and neurological deficit [52] . In view of these complex spatiotemporal developments in MCA stroke, a refined schematic classification of stroke types is proposed, building on the classification of Donnan and coworkers originally based on radiological findings [50].
This classification takes on particular importance in the present context because type of stroke injury may influence features of post-stroke brain reorganization and recovery.
If reperfusion is achieved early, only the deep perforating arteries and the arteries supplying the insular cortex remain critically affected by ischemic infarcts limited to the lens nucleus and insula (Figure 9.3). Such infarcts are more limited in impact, and thus provide a profound regression of the initial neurological deficit and marked recovery over the following weeks [64]. Conversely, in the case of delayed or absent reperfusion of the MCA, the infarct becomes larger, including the adjacent periventricular white matter in addition to the striatum and insula (Figure 9.3).
Understanding the pathogenesis of cerebral injury from stroke may be important for understanding and treating brain repair after stroke. Co-registration of acute PWI, acute DWI and subacute fMRI activation data related to sequential finger movements of the affected/recovered hand. Note that activation of sensorimotor cortex in the affected hemisphere is in an area of previous perfusion-diffusion mismatch [48].
These observations suggest that the acute macrovascular occlusion of the MCA that causes the acute neurologic stroke syndrome may cause a particularly devastating perfusion deficit when a compensatory redistribution of arterial blood along collaterals is impaired. Nevertheless, using statistical parametric mapping, it has been shown that in patients with more severe cerebral infarction, the hemispheric white matter is broad. On this basis, white matter involvement is hypothesized to be the cause of neuropsychological disorders such as hemispatial neglect and conduction aphasia [71,72] (see Chapters 12 and 13).
The greater injury of type II strokes means greater behavioral deficits, and less available tissue to contribute to post-stroke reorganization, exacerbated by disconnection due to white matter injury.
Such patients experience a particularly severe stroke with large areas of severely reduced perfusion, resulting in extensive brain damage and limited recovery [43,65,66]. In fact, an ischemic event in addition to acute occlusion of the MCA or ICA appears to result from widespread arterial changes such as vessel stenosis or occlusion in multiple cerebral arteries [43].
Thalamic metabolism and pyramidal tract integrity determine motor recovery in stroke. Ann Neurol. Given the complexity of the events following a TMS pulse, it is not surprising that the results reported in the literature have been relatively variable (see Talelli et al. for review [4]). TMS has been used to characterize a variety of inter-regional interactions from non-primary motor regions targeting the motor cortex in healthy humans, and their roles in relation to various aspects of movement (see Reis et al. for review [42] ).
Motor disinhibition in the affected and unaffected hemisphere in the early recovery period after stroke. Clin. For example, cerebrovascular reactivity in the patient's right hemisphere was studied by Rötheret al. Relationship between cerebral activity and strength in motor areas of the human brain. J Neurophysiol.
Predicting the response to citalopram and reboxetine in post-stroke depressed patients. Psychopharmacology (Berl). For example, Stinear et al., who studied 21 patients with chronic stroke, showed that integrity of the corticospinal tracts as measured by fractional anisotropy (FA) with diffusion tensor imaging can be used to predict response to therapy for people with motor deficits have [49]. Future of neuroprotection for acute stroke: In the wake of the SAINT trials.Ann Neurol.
In the next part of the chapter, we will describe the interest of neuroimaging in more detail. The first study on the effects of amphetamine on stroke recovery in humans [10] was carefully designed to simulate the paradigm used in the laboratory.
