Ischemia was first reported as one of the crucial pathophysiological mechanisms in CSM by brain [
6]. Evidence stemming from animal and human studies supports this theory. Specifically, pathological changes such as vessel wall thickening and hyalinization have been identified in the anterior spinal artery and parenchymal arterioles [
6,
7] while the radiculomedullary arterial diameter is compromised by stenosis of the intervertebral foramina in patients with CSM [
8]. Additional histopathological indications of ischemic injury in the gray and white matter of the cord have been observed in patients with CSM [
9,
10]. Findings from a cadaveric study, where terminal branches of the anterior spinal artery and penetrating branches of the lateral pial plexus were observed to be curved and stretched around degenerative spinal spondylo-osteophytes, support the suggestion of compromised blood flow to axonal pathways including the corticospinal tracts [
10]. Experimental work has provided indirect evidence suggesting ischemia in animals suffering from CSM in that angiography studies in animal models suffering from CSM revealed signs of compromised perfusion. Other investigators have studied the combined insult of direct compression and ischemia to the cord. Overall, ischemia seems to heighten the insult of cord compression [
11], and changes in blood flow to the spinal cord [
12]. In this setting, the corticospinal tract is the most affected part of cord [
11], which fits the clinical presentation in CSM [
5]. In one other experimental protocol, the direct compression of specific spinal arteries caused diminished blood flow to the respective arteries feeding that part of the spine [
13]. Taylor suggested that radiculomedullary arteries supplying the cervical spinal cord were compromised by stenosis of the intervertebral foramina [
8]. A pathophysiologic explanation is that age-related degenerative changes in the cervical spine can compress major feeding arteries like the vertebral artery [
14], anterior spinal artery and its ventral branches, or the radicular arteries of the neuroforamina [
7,
15]. As a result, the blood flow velocity within vertebral arteries can be pathologically reduced [
16] while perfusion to key parts of the spinal cord is compromised [
16]. Moreover, spondylotic deformations of the cervical spine such as kyphosis have been identified to be involved in the onset or the progression of the disease by interfering with the spinal cord vascular network [
17,
18]. This necessitates the careful evaluation not only of the cervical alignment but also of the global spinal alignment before the appropriate surgical approach will be decided [
19].
In the past, the lack of a reliable animal model of induced CSM has led to uncertainty regarding the role of ischemia in CSM, but also of the existence of microvasculature distortion under chronic and progressive compression of the cervical spinal cord. Using a series of arguments, different groups have expressed their uncertainty as to whether ischemia is a crucial physiological event in CSM. Specifically, a number of clinical and experimental protocols demonstrate that patients or laboratory animals with moderate CSM have no [
21] or only mild signs of ischemia [
22,
23] while pathologic evidence of ischemia is found only when severe canal stenosis is coexisting [
24,
25]. Moreover, some experimental studies found only minor changes in blood flow during compression and decompression [
26]. In addition, another group using a computational model of cervical spinal cord compression predicted no compromise of blood flow in the intramedullary blood vessels. From a molecular standpoint, one of the principal arguments against the significant pathobiological role of ischemia in CSM is that ischemia, despite eliciting an apoptotic response, usually leads to cellular death via necrosis and not through the apoptotic pathway. Evidence indicating that the oligodendrocyte and neuronal cell death, that has been demonstrated in human and experimental studies, appears to be a result of apoptosis has fuelled the argument against the role of ischemic injury in CSM from some groups.
Summarizing, some of the above-described studies display significant merit, however, they present with critical limitations, which means that we do not yet have the answer regarding the role for chronic ischemia in CSM. Most of these studies have been performed in animal models where the compression is acute or sub-acute in nature and, therefore, fail to reproduce the chronic and progressive compression seen in human CSM. Moreover, many of these models entail compression not in the cervical spinal cord, but in the thoracic area. These limitations leave a gap necessitating the study of the spinal cord blood flow in experimental models which are characterized by slow progressive compression at the C5–C6 level [
27,
28].