The prognostic value of collateral circulation in coronary chronic total occlusion underwent percutaneous coronary intervention

BACKGROUND The prognostic value of coronary collateral circulation(CC)in patients undergoing chronic total occlusion(CTO)percutaneous coronary intervention(PCI)is underdetermined.The purpose of the study was to assess the prognostic value of current two CC grading systems and their association with long-term outcomes in patients with CTO underwent PCI.METHODS We consecutively enrolled patients with single-vessel CTO underwent PCI between January 2010 and December2013.All patients were categorized into well-developed or poor-developed collaterals group according to angiographic Werner's CC(grade 2 vs.grade 0–1)or Rentrop(grade 3 vs.grade 0–2)grading system.The primary endpoint was 5-year cardiac death.RESULTS Of 2452 enrolled patients,the overall technical success rate was 74.1%.Well-developed collaterals were present in686 patients(28.0%)defined by Werner's CC grade 2,and in 1145 patients(46.7%)by Rentrop grade 3.According to Werner's CC grading system,patients with well-developed collaterals had a lower rate of 5-year cardiac death compared with those with poordeveloped collaterals(1.6%vs.3.3%,P=0.02),those with suboptimal recanalization was associated with higher rate of 5-year cardiac death compared with optimal recanalization(4.7%vs.0.8%,P=0.01)and failure patients(4.7%vs.1.6%,P=0.12).However,the similar effect was not shown in Rentrop grading system.CONCLUSIONS In patients with the single-vessel CTO underwent PCI,well-developed collaterals by Werner's CC definition were associated with lower rate of 5-year cardiac death.Werner's CC grading system had a greater prognostic value than Rentrop grading system in patients with CTO underwent PCI.

Clinical Nursing Intervention of Moxibustion on Abdominal Distension Symptoms in Heart Failure (Heart and Kidney Yang Deficiency and Blood Stasis Blocking Collaterals Syndrome)

Objective:To investigate the clinical nursing intervention effect of moxibustion on abdominal distension symptoms in heart failure(heart and kidney yang deficiency and blood stasis blocking collaterals syndrome).Methods:62 patients with heart failure(heart and kidney yang deficiency and blood stasis blocking collaterals syndrome)admitted to our hospital from February 2023 to February 2024 were selected and divided into the observation group(n=31)and the control group(n=31)by using the random numerical table method.The control group adopted conventional nursing interventions,and the observation group received the nursing program of the control group with the addition of moxibustion nursing interventions.The nursing effectiveness,quality of life scores,and nursing satisfaction were compared between the two groups.Results:The nursing effectiveness of the observation group was significantly higher than the control group(P<0.05);the quality of life score of the observation group was significantly higher than the control group(P<0.05);the nursing satisfaction of the observation group was significantly higher than that of the control group(P<0.05).Conclusion:The use of moxibustion nursing intervention in patients with heart failure(heart and kidney yang deficiency and blood stasis blocking collaterals syndrome)can effectively relieve the symptoms of abdominal distension,improve patients'quality of life,and increase nursing satisfaction,which has promotion and application values.

Advances in Research of Treatment of Angina Pectoris in Coronary Heart Disease from the Method of Dredging Collaterals with Pungent

The angina pectoris in coronary heart disease belongs to the category of"chest impediment"in traditional Chinese medicine,and belongs to the syndrome of root deficiency with tip excess.Its main pathogenesis is obstruction of the heart collaterals,and treatment mainly adopts dredging collaterals and relieving pain.Based on the treatment principles of dredging collaterals with pungent,aiming at the etiology,pathogenesis and disease characteristics of angina pectoris in coronary heart disease,this article systematically analyzes the Method of Dredging Collaterals with Pungent including the methods of dredging collaterals with pungent moisture,dredging collaterals with pungent warm,dredging collaterals with pungent aroma,and dredging collaterals with insect type drugs,to provide ideas for the treatment of angina pectoris in coronary heart disease.

Promotion effect of TGF-β-Zfp423-ApoD pathway on lip sensory recovery after nerve sacrifice caused by nerve collateral compensation

Resection of oral and maxillofacial tumors is often accompanied by the inferior alveolar nerve neurectomy,resulting in abnormal sensation in lower lip.It is generally believed that spontaneous sensory recovery in this nerve injury is difficult.However,during our follow-up,patients with inferior alveolar nerve sacrifice showed different degrees of lower lip sensory recovery.In this study,a prospective cohort study was conducted to demonstrate this phenomenon and analyze the factors influencing sensory recovery.

Isolated Major Aortopulmonary Collateral Artery Causing Heart Failure: Transcatheter Occlusion of Mapcas Using Amplatzer Vascular Plugs and Amplatzer Piccolo Occluders

Major aortopulmonary collateral arteries (MAPCAs) are congenital vessels that arise from the aorta or its first-order branches and are distally connected to the pulmonary arterial vasculature, thereby providing pulmonary blood flow. MAPCAs are often associated with cyanotic congenital heart disease with decreased pulmonary blood flow. Isolated MAPCAs are rare in patients without congenital heart disease with structurally normal hearts. Sometimes, isolated congenital MAPCAs can occur without any lung disease. Isolated MAPCAs represent the occurrence of collaterals in the absence of underlying heart disease, which commonly presents as heart failure, recurrent respiratory tract infection, and pulmonary artery hypertension. We report a rare case of congestive heart failure in a 6-year-old patient with dual arterial supply to an otherwise normal right lung, with a normal bronchial tree, and a structurally normal heart. The patient was successfully managed by the closure of collaterals by Amplatzer vascular plugs II (AVPII) and Amplatzer Piccolo Occluders.

Discussion on reprogramming of tumor energy metabolism and intervention of traditional Chinese medicine based on the theory of“collateral Q i stagnation”

The theory of stagnation of collateral Qi(Chinese medicine refers to the most fundamental and subtle substances thatconstitute the human body and maintain life activities,and also has the meaning of physiological functions)originates from the theory of collateral disease,which refers to the deficiency of Qi in the body’s collaterals,the loss of Qi and blood,and the failure of stagnation of collateral Qi,which leads to the loss of Qi,blood and body fluid,and the formation of pathological products such as deficiency,depression,phlegm,blood stasis in the local area,and ultimately damage the pathological process of collaterals.Based on the in-depth study of the pathogenesis of collateral Qi stagnation and the previous study of meridian channels,we believe that the key pathogenesis of the formation,evolution and spread of malignant tumors is“collateral Qi deficiency stagnation,collateral Qi stagnation and collateral Qi decay”.As an important energy resonance channel of the body,meridians play a key role in the process of material transformation and energy metabolism.It is believed that the small focus caused by the pathogenesis of stagnation is the cause of malignant transformation of tumor,the reprogramming of energy metabolism induced by the lesion of collateral Qi is the basis of the progress of tumor pathogenesis,and the formation of tumor microenvironment regulated by the tumor toxin vena is the root of alienation of tumor development.Guided by this theory,focusing on the correlation between collateral Qi and tumor energy metabolism,using Professor Hua Baojin's treatment method of“Regulating Qi and detoxifying”to prescribe drugs can adjust collateral Qi function,achieve the relative balance of internal environment,and then inhibit the progress of tumor.Based on the above understanding,this study tries to enlighten new diagnosis and treatment ideas under the guidance of“stagnation of collateral Qi”in traditional Chinese medicine,in order to provide some theoretical support for the intervention of traditional Chinese medicine in the process of tumor development.

Electroacupuncture improves neurovascular unit reconstruction by promoting collateral circulation and angiogenesis

Acupuncture at Shuigou（GV26） shows good clinical efficacy for treating stroke, but its mechanism remains poorly understood. In this study, a cerebral infarction model of ischemia/reperfusion injury received electroacupuncture at GV26（15 Hz and 1 m A, continuous wave [biphasic pulses], for 5 minutes）. Electroacupuncture effectively promoted regional cerebral blood flow on the infarct and non-infarct sides, increased infarct lesions, lectin, and number of blood vessels, upregulated von Willebrand factor and cell proliferation marker Ki67 expression, and diminished neurological severity score. These findings confirm that electroacupuncture at GV26 promotes establishment of collateral circulation and angiogenesis, and improves neurological function.

64-row multidetector computed tomography portal venography of gastric variceal collateral circulation

AIM:To study characteristics of collateral circulation of gastric varices (GVs) with 64-row multidetector computer tomography portal venography (MDCTPV).METHODS:64-row MDCTPV with a slice thickness of 0.625 mm and a scanning field from 2 cm above the tracheal bifurcation to the lower edge of the kidney was performed in 86 patients with GVS diagnosed by endoscopy. The computed tomography protocol included unenhanced,arterial and portal vein phases. The MDCTPV was performed on an AW4.3 workstation. GVs were classified into three types according to Sarin's Classification. The afferent and efferent veins of each type of GV were observed.RESULTS:The afferent venous drainage originated mostly from the left gastric vein alone (LGV) (28/86,32.59%),or the LGV more than the posterior gastric vein/short gastric vein [LGV > posterior gastric vein/short gastric vein (PGV/SGV)] (22/86,25.58%),as seen by MDCTPV. The most common efferent venousdrainage was via the azygos vein to the superior vena cava (53/86,61.63%),or via the gastric/splenorenal shunt (37/86,43.02%) or inferior phrenic vein (8/86,9.30%) to the inferior vena cava. In patients with gastroesophageal varices type 1,the afferent venous drainage of GV mainly originated from the LGV or LGV > PGV/SGV (43/48,89.58%),and the efferent venous drainage was mainly via the azygos vein to the super vena cava (43/48,89.58%),as well as via the gastric/splenorenal shunt (8/48,16.67%) or inferior phrenic vein (3/48,6.25%) to the inferior vena cava. In patients with gastroesophageal varices type 2,the afferent venous drainage of the GV mostly came from the PGV/SGV more than the LGV (PGV/SGV > LGV) (8/16,50%),and the efferent venous drainage was via the azygos vein (10/16,62.50%) and gastric/splenorenal shunt (9/16,56.25%). In patients with isolated gastric varices,the main afferent venous drainage was via the PGV/SGV alone (16/22,72.73%),and the efferent venous drainage was mainly via the gastric/splenorenal shunt (20/22,90.91%),as well as the inferior phrenic vein (3/23) to the inferior vena cava. CONCLUSION:MDCTPV can clearly display the afferent and efferent veins of all types of GV,and it could provide useful reference information for the clinical management of GV bleeding.

Contralateral needling at unblocked collaterals for hemiplegia following acute ischemic stroke

Hemiplegia caused by stroke indicates dysfunction of the network between the brain and limbs, namely collateral shock in the brain. Contralateral needling is the insertion of needles into acupoints on the relative healthy side of the body to treat diseases such as apoplexy. However, there is little well-designed and controlled clinical evidence for this practice. This study investigated whether contralateral needling could treat hemiplegia after acute ischemic stroke in 106 randomly selected patients with acute ischemic stroke. These patients were randomly assigned to three groups： 45 in the contralateral needling group, receiving acupuncture on the unaffected limbs; 45 in the conven- tional acupuncture group, receiving acupuncture on the hemiplegic limbs; and 16 in the control group, receiving routine treatments without acupuncture. Acupuncture at acupoints Chize （LU5） in the upper limb and Jianliao （TEl4） in the lower limb was performed for 45 minutes daily for 30 consecutive days. The therapeutic effective rate, Neurological Deficit Score, Modified Barthel Index and FugI-Meyer Assessment were evaluated. The therapeutic effective rate of contralateral nee- dling was higher than that of conventional acupuncture （46.67% vs. 31.11%, P 〈 0.05）. The neuro- logical deficit score of contralateral needling was significantly decreased compared with conven- tional acupuncture （P 〈 0.01）. The Modified Barthel Index and FugI-Meyer Assessment score of contralateral needling increased more significantly than those of conventional acupuncture （both P 〈 0.01）. The present findings suggest that contralateral needling unblocks collaterals and might be more effective than conventional acupuncture in the treatment of hemiplegia following acute ischemic stroke.

Portal hypertension: Imaging of portosystemic collateral pathways and associated image-guided therapy

Portal hypertension is a common clinical syndrome, defined by a pathologic increase in the portal venous pressure. Increased resistance to portal blood flow, the primary factor in the pathophysiology of portal hypertension, is in part due to morphological changes occurring in chronic liver diseases. This results in rerouting of blood flow away from the liver through collateral pathways to low-pressure systemic veins. Through a variety of computed tomographic, sonographic, magnetic resonance imaging and angiographic examples, this article discusses the appearances and prevalence of both common and less common portosystemic collateral channels in the thorax and abdomen. A brief overview of established interventional radiologic techniques for treatment of portal hypertension will also be provided. Awareness of the various imaging manifestations of portal hypertension can be helpful for assessing overall prognosis and planning proper management.

Coronary collateral circulation： Effects on outcomes of acute anterior myocardial infarction after primary percutaneous coronary intervention

Background To investigate the effects of collateral coronary circulation on the outcome of the patients with anterior myocardial infarction （MI） with left anterior desending artery occlusion abruptly. Methods Data of 189 patients with acute anterior MI who had a primary percutaneous coronary intervention （PCI） in the first 12 h from the onset of symptoms between January 2004 and December 2008 were retrospective analyzed. Left anterior descending arteries （LAD） of all patients were occluded. LADs were reopened with primary PCI. According to the collateral circulation, all patients were classified to two groups： no collateral group （n = 111）, patients without angiographic collateral filling of LAD or side branches （collateral index 0） and collateral group （n = 78）, and patients with angiographic collateral filling of LAD or side branches （collateral index 1, 2 or 3）. At one year＇ s follow-up, the occurrence of death, reinfarctlon, stent thrombosis （ST）, target vessel revascularization and readmission because of heart failure were observed. Results At one year, the mortality was lower in patients with collateral circulation compared with those without collateral circulation （1% vs. 8%, P = 0.049）, whereas there Were no differences in the occurrence of reinfarction, ST, target vessel revascularization and readmission because of heart failure. The occurrence of composite of endpoint was lower in patients with collateral circulation compared with those without collateral circulation （12% vs. 26%; P = 0.014）. Conclusions Pre-exist collateral circulation may prefigure the satisfactory prognosis to the patients with acute anterior MI after primary PCI in the first 12 h of MI onset.

Extrahepatic collaterals and liver damage in embolotherapy for ruptured hepatic artery pseudoaneurysm following hepatobiliary pancreatic surgery

AIM: To evaluate the effects of extrahepatic collaterals to the liver on liver damage and patient outcome after embolotherapy for the ruptured hepatic artery pseudoa- neurysm following hepatobiliary pancreatic surgery. METHODS: We reviewed 9 patients who underwent transcatheter arterial embolization (TAE) for the ruptured hepatic artery pseudoaneurysm following major hepato- biliary pancreatic surgery between June 1992 and April 2006. We paid special attention to the extrahepatic arte- rial collaterals to the liver which may affect post-TAE liver damage and patient outcome. RESULTS: The underlying diseases were all malignan- cies, and the surgical procedures included hepatopancre- atoduodenectomy in 2 patients, hepatic resection with removal of the bile duct in 5, and pancreaticoduodenec- tomy in 2. A total of 11 pseudoaneurysm developed: 4 in the common hepatic artery, 4 in the proper hepatic artery, and 3 in the right hepatic artery. Successful he- mostasis was accomplished with the initial TAE in all patients, except for 1. Extrahepatic arterial pathways to the liver, including the right inferior phrenic artery, the jejunal branches, and the aberrant left hepatic artery, were identified in 8 of the 9 patients after the completion of TAE. The development of collaterals depended on the extent of liver mobilization during the hepatic resection, the postoperative period, the presence or absence of an aberrant left hepatic artery, and the concomitant arte- rial stenosis adjacent to the pseudoaneurysm. The liver tolerated TAE without significant consequences when at least one of the collaterals from the inferior phrenic ar-tery or the aberrant left hepatic artery was present. One patient, however, with no extrahepatic collaterals died of liver failure due to total liver necrosis 9 d after TAE. CONCLUSION: When TAE is performed on ruptured hepatic artery pseudoaneurysm, reduced collateral path- ways to the liver created by the primary surgical proce- dure and a short postoperative interval may lead to an unfavorable outcome.

Inferior vena cava obstruction and collateral circulation as unusual manifestations of hepatobiliary cystadenocarcinoma

BACKGROUND: Hepatobiliary cystadenocarcinoma represents a rare epithelial malignant tumor derived from the intrahepatic bile duct. METHODS: A 71-year-old woman, who had undergone laparoscopic drainage of a cystic lesion of the right hepatic lobe, was misdiagnosed as having hepatic echinococcal disease, and received intracystic infusion of 95% ethanol four years ago. She was admitted to our hospital for further treatment. RESULTS: Physical examination revealed dilated superficial veins across the right abdominal wall. After mapping the direction of blood flow in these vessels, we assumed that this was a sign of inferior vena cava obstruction. Abdominal ultrasound, computed tomography, magnetic resonance imaging combined with magnetic resonance angiography showed a large cystic mass in the right upper quadrant and epigastrium, displacing the adjacent structures, adherent to the inferior vena cava, which was not patent, resulting in dilation of superficial epigastric veins. The patient underwent an exploratory laparotomy. Total excision of the huge mass measuring 16×15 cm was possible under selective vascular exclusion of the liver. Removal of the tumor resulted in immediate restoration of flow in the inferior vena cava. On the basis of the pathology and findings of immunohistochemical analysis, a hepatobiliary cystadenocarcinoma was diagnosed.CONCLUSIONS: In the present case, hepatobiliary cystadenocar-cinoma was accompanied by dilated superficial venous collaterals due to inferior vena cava obstruction. Selective vascular exclusion of the liver allowed a safe oncological resection of the tumor.

Understanding the medial ulnar collateral ligament of the elbow: Review of native ligament anatomy and function

The medial ulnar collateral ligament complex of the elbow, which is comprised of the anterior bundle [AB, more formally referred to as the medial ulnar collateral ligament(MUCL)], posterior(PB), and transverse ligament, is commonly injured in overhead throwing athletes. Attenuation or rupture of the ligament results in valgus instability with variable clinical presentations. The AB or MUCL is the strongest component of the ligamentous complex and the primary restraint to valgus stress. It is also composed of two separate bands(anterior and posterior) that provide reciprocal function with the anterior band tight in extension, and the posterior band tight in flexion. In individuals who fail co-mprehensive non-operative treatment, surgical repair or reconstruction of the MUCL is commonly required to restore elbow function and stability. A comprehensive understanding of the anatomy and biomechanical properties of the MUCL is imperative to optimize reconstructive efforts, and to enhance clinical and radiographic outcomes. Our understanding of the native anatomy and biomechanics of the MUCL has evolved over time. The precise locations of the origin and insertion footprint centers guide surgeons in proper graft placement with relation to bony anatomic landmarks. In recent studies, the ulnar insertion of the MUCL is described as larger than previously thought, with the center of the footprint at varying distances relative to the ulnar ridge, joint line, or sublime tubercle. The purpose of this review is to consolidate and summarize the existing literature regarding the native anatomy, biomechanical, and clinical significance of the entire medial ulnar collateral ligament complex, including the MUCL(AB), PB, and transverse ligament.

Effect of Salvia Miltiorrhiza on Coronary Collateral Circulation in Dogs with Experimental Acute Myocardial Infarction

Summary: To evaluate the effect of Salvia Miltiorrhiza on coronary collateral circulation in dogs with experimental acute myocardial infarction, 12 dogs were randomly divided into Salvia Miltiorrhiza group (group D) and control group (group C). Acute myocardial infarction model was established in all dogs, Salvia Miltiorrhiza or saline was administered to the 2 groups respectively for 21 days. Coronary angiography was performed before and after ligation of coronary artery. The capillaries and distribution vessel density in tissue sections of myocardia were assessed. Angiography 2 h and 22 days after ligation of coronary artery revealed significant augmentation of collateral vessels, and capillaries and distribution vessel density in ischemic zone on day 22 showed statistically significant augmentation in group D as compared with that of controls ( P <0. 05 and P <0. 01). It is concluded that Salvia Miltiorrhiza might improve the opening and formation of coronary collateral circulation of ischemic myocardia in dogs and thereby protecting myocardia from ischemia.

Acute development of collateral circulation and therapeutic prospects in ischemic stroke

In acute ischemic stroke,collateral circulation plays an important role in maintaining blood flow to the tissue that is at risk of progressing into ischemia,and in increasing the successful recanalization rate without hemorrhagic transformation.We have reported that well-developed collateral circulation is associated with smaller infarct volume and better long-term neurological outcome,and it disappears promptly once the effective recanalization is achieved.Contrary to the belief that collateral vessels develop over time in chronic stenotic condition,there exists a phenomenon that collateral circulation develops immediately in acute stenosis or occlusion of the arteries and it seems to be triggered by fluid shear stress,which occurs between the territories of stenotic/occluded arteries and those fed by surrounding intact arteries.We believe that this acute development of collateral circulation is a target of novel therapeutics in ischemic stroke and refer our recent attempt in enhancing collateral circulation by modulating sphingosine-1-phosphate receptor 1,which is a known shear-stress mechanosensing protein.

Diagnosis and outcomes of collateral arterial formation after irreversible early hepatic artery thrombosis in pediatric liver recipients

BACKGROUND： Early hepatic artery thrombosis （eHAT） has been recognized as an important cause of graft loss and mortality. However, the incidence, etiology and outcome are not dear, especially for children. The present study was to investigate the formation of collateral artery flow after irreversible eHAT and its impact on patient＇s prognosis. METHODS： We analyzed eHAT after liver transplantation in children from October 2006 to April 2015 in our center, illustrated the formation of collateral hepatic artery flow after irreversible eHAT and explored the diagnosis, complications, treatment and prognosis. The basic and follow-up ultrasonographic images were also compared. RESULTS： Of the 330 pediatric liver recipients, 22 （6.67%） de- veloped eHAT within 1 month. Revascularization attempts in- duding surgical thrombectomy, interventional radiology and conservational treatment （thrombolysis） were successful in 5 patients. Among the 17 patients who had irreversible eHAT, follow-up ultrasonography revealed that collateral artery flow was developed as early as 2 weeks after eHAT. Liver abscess and bile duct complication occurred secondary to eHAT in variable time. CONCLUSIONS： Collateral arterial formation is a compensatory adaptation to eHAT to supply blood to liver grafts. However, the severe bile duct damage secondary to eHAT is irreversible and retransplantation is unavoidable.

Successful occluding by absorbable sutures for epicardial collateral branch perforation

In order to improve the success rate of chronic total occlusion (CTO)percutaneous coronary intervention (PCI), retrograde approach has been attracted more attention.Recent study reported the collateral perforation rate was 6.9% in retrograde CTO PCI.[1,2] Collateral related perforations were higher in patients with the epicardial collateral than that with the septal collateral.[3]Several techniques have been developed to deal with the collateral branch perforation.Here,we described the treatment of epicardial collateral branch perforation by absorbable suture segments embolization through microcatheter during retrograde CTO PCI.

Association of atherosclerotic plaque features with collateral circulation status in elderly patients with chronic carotid stenosis

Objective To determine the association of carotid plaque features with collateral circulation status in elderly patients with moderate to severe carotid stenosis.Methods Elderly patients(>60 years)with moderate to severe carotid stenosis were recruited and categorized into good and poor collateral circulation groups,and underwent magnetic resonance imaging and computed tomography imaging.The carotid plaque features including lipid-rich necrotic core,intraplaque hemorrhage,calcification,and fibrous cap rupture(FCR)were evaluated,and maximum wall thickness,normalized wall index(NWI),and luminal stenosis were measured.The association between these variables and collateral circulation status was analyzed.Results Of the 97 patients(78 males,mean age:69.0±6.1 years),19(19.6%)had poor collaterals.The poor collateral group had a significantly higher NWI(93.7%±5.0%vs.89.0%±7.9%,P=0.011),a greater extent of stenosis(80.0%±11.4%vs.75.3%±9.4%,P=0.036)and FCR(84.2%vs.55.1%,P=0.020)compared with good collateral group.Carotid NWI(OR=3.83,95%CI:1.36–10.82,P=0.011)and more FCR(OR=6.77,95%CI:1.35–33.85,P=0.020)were associated with poor collateral circulation after adjustment for the confounding factors.The combination of NWI,FCR,systolic blood pressure,and triglycerides had the highest area-under-the-curve(AUC=0.85)for detection of poor collaterals.Conclusions Carotid plaque features,specifically NWI and FCR,are independently associated with poor collateral circulation,and the combination of carotid plaque features and traditional risk factors has a stronger predictive value for poor collateral circulation than plaque features alone.

New insights on the molecular mechanisms of collateral sprouting after peripheral nerve injury

Axonal regeneration after injuries to the nervous system has been extensively studied due to its implication in motor and sensory functional recovery. Distinct types of regeneration has been identified, such as canonical axonal regeneration, defined as the growth of axons from the transected axonal stump to reinnervate the original target, or regenerative sprouting, in which the growth occurs from a region of the damaged axon either close or far from the injury site(Tuszynski and Steward, 2012).