Midkine (MK) is a growth factor with neurotrophic and neurite outgrowth activities. It was expressed in the peri-ischaemic area in the acute phase of cerebral infarction in rat brains. Astrocytes were the origin of MK in this occasion. MK has been assessed in terms of its effects on neural injury. The administration of MK into the lateral ventricle immediately prior to ischaemia prevented cell death in the hippocampal CA1 neurons degenerated by transient forebrain ischaemia in gerbils. MK administration was also beneficial in rats with neural injury, especially after kainic acid-induced seizures. Gene therapy with mouse MK cDNA using an adenovirus was effective in reducing the cerebral infarction volume and in increasing the number of neuronal precursor cells in the subventricular zone of the rat brain. MK mRNA and MK protein were found in spinal cord motor neurons of the anterior horn in both the acute phase of sciatic nerve injury and 3 weeks later. MK immunoreactivity was also found in the proximal side of a sciatic nerve-injured site in sciatic nerve axons. MK receptors were expressed in Schwann cells after injury, suggesting crosstalk between axons and Schwann cells. MK was also present in nerve terminals and influenced ACh receptor clustering during neuromuscular development in Xenopus. Thus, MK may also be involved in reinforcing and maintaining the synapse. All these findings indicate the therapeutic potential of MK for promoting repair of the nervous system after injury.LINKED ARTICLESThis article is part of a themed section on Midkine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-4

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Midkine (MK) is a growth factor implicated in the development and repair of various tissues, especially neural tissues. MK acts as a reparative neurotrophic factor in damaged peripheral nerves. A postulated role of MK in the degeneration and regeneration of sciatic nerves was explored by comparing wild-type (Mdk(+/+)) mice with MK-deficient (Mdk(-/-)) mice after freezing injury. In the Mdk(-/-) mice, a regenerative delay was observed, preceded by a decelerated Wallerian degeneration (WD). The relative wet weight of the soleus muscle slowly declined, and recovery was delayed compared with that in the Mdk(+/+) mice. In the regenerating nerve, unmyelinated axons were unevenly distributed, and some axons contained myelin-like, concentrically lamellated bodies. In the endplates of soleus muscles, nerve terminals containing synaptic vesicles disappeared in both mice. In Mdk(-/-) mice, the appearance of nerve terminals was delayed in synaptic vesicles of terminal buttons after injury. The recovery of evoked electromyogram was delayed in Mdk(-/-) mice compared with Mdk(+/+) mice. Our results suggested a delay in axonal degeneration and regeneration in Mdk(-/-) mice compared with Mdk(+/+) mice, and the delayed regeneration was associated with a delayed recovery of motor function. These findings show that a lack of MK following peripheral nerve injury is a critical factor in degeneration and regeneration, and manipulation of the supply of MK may offer interesting therapeutic options for the treatment of peripheral nerve damage.

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