Effects of neuregulin-1 on autonomic nervous system remodeling post-myocardial infarction in a rat model

Sympathetic nerve and vagus nerve remodeling play an important part in cardiac function post-myocardial infarction （MI）. Increasing evidence indicates that neuregulin-1 （NRG-1） improves cardiac function following heart failure. Since its impact on cardiac function and neural remodeling post-MI is poorly understood, we aimed to investigate the role of NRG-1 in autonomic nervous system remodeling post-MI. Forty-five Sprague-Dawley rats were equally randomized into three groups： sham （with the left anterior descending coronary artery exposed but without ligation）, MI （left anterior descending coronary artery ligation）, and MI plus NRG-1 （left anterior descending coronary artery ligation followed by intraperitoneal injection of NRG-1 （10 lag/kg, once daily for 7 days））. At 4 weeks after MI, echocardi- ography was used to detect the rat cardiac function by measuring the left ventricular end-systolic inner diameter, left ventricular diastolic diameter, left ventricular end-systolic volume, left ventricular end-diastolic volume, left ventricular ejection fraction, and left ventricular fractional shortening, mRNA and protein expression levels of tyrosine hydroxylase, growth associated protein-43 （neuronal specific pro- tein）, nerve growth factor, choline acetyltransferase （vagus nerve marker）, and vesicular acetylcholine transporter （cardiac vagal nerve fiber marker） in ischemic myocardia were detected by real-time PCR and western blot assay to assess autonomous nervous remodeling. After MI, the rat cardiac function deteriorated significantly, and it was significantly improved after NRG-1 injection. Compared with the MI group, mRNA and protein levels of tyrosine hydroxylase and growth associated protein-43, as well as choline acetyltransferase mRNA level significantly decreased in the MI plus NRG-1 group, while mRNA and protein levels of nerve growth factor and vesicular acetylcholine transporters, as well as choline acetyltransferase protein level slightly decreased. Our results indicate that NRG- 1 can improve cardiac function and regulate sympathetic and vagus nerve remodeling post-MI, thus reaching a new balance of the autonomic nervous system to protect the heart from injury.

Short-term observations of the regenerative potential of injured proximal sensory nerves crossed with distal motor nerves

Motor nerves and sensory nerves conduct signals in different directions and function in different ways.In the surgical treatment of peripheral nerve injuries,the best prognosis is obtained by keeping the motor and sensory nerves separated and repairing the nerves using the suture method.However,the clinical consequences of connections between sensory and motor nerves currently remain unknown.In this study,we analyzed the anatomical structure of the rat femoral nerve,and observed the motor and sensory branches of the femoral nerve in the quadriceps femoris.After ligation of the nerves,the proximal end of the sensory nerve was connected with the distal end of the motor nerve,followed by observation of the changes in the newly-formed regenerated nerve fibers.Acetylcholinesterase staining was used to distinguish between the myelinated and unmyelinated motor and sensory nerves.Denervated muscle and newly formed nerves were compared in terms of morphology,electrophysiology and histochemistry.At 8 weeks after connection,no motor nerve fibers were observed on either side of the nerve conduit and the number of nerve fibers increased at the proximal end.The proportion of newly-formed motor and sensory fibers was different on both sides of the conduit.The area occupied by autonomic nerves in the proximal regenerative nerve was limited,but no distinct myelin sheath was visible in the distal nerve.These results confirm that sensory and motor nerves cannot be effectively connected.Moreover,the change of target organ at the distal end affects the type of nerves at the proximal end.

Neural regeneration after peripheral nerve injury repair is a system remodelling process of interaction between nerves and terminal effector

In China, there are approximately 20 million people suffering from peripheral nerve injury and this number is increasing at a rate of 2 million per year. These patients cannot live or work independently and are a heavy responsibility on both family and society because of extreme disability and dysfunction caused by peripheral nerve injury （PNI）. Thus, repair of PNI has become a major public health issue in China.